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Explanation and Elaboration for the ARRIVE Guidelines 2.0—Reporting Animal Research and In Vivo Experiments (Ⅰ) Jian WANG, Jin LU, Zhengwen MA, Guoyuan CHEN, Xiao LU, Yu BAI, Xiaoyu LIU, Xuancheng LU, Jing GAO, Yao LI, Wanyong Pang Laboratory Animal and Comparative Medicine    2023, 43 (2): 213-224.   DOI: 10.12300/j.issn.1674-5817.2023.043 Abstract （2079）   HTML （83）    PDF （1622KB）（4734）       Knowledge map    Save Improving the reproducibility of biomedical research results is a major challenge. Researchers reporting their research process transparently and accurately can help readers evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. this article is a Chinese translation based on the best practices of international journals following the ARRIVE 2.0 guidelines in international journals, specifically for the complete interpretation of the ARRIVE 2.0 guidelines published in the PLoS Biology journal in 2020 (original text can be found at https://arriveguidelines.org ). The first part of the article includes the preface and the "Key 10" section, which covers "study design" "sample size" and "inclusion and exclusion criteria". Its aim is to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhance the standardization of experimental animal research and reporting, and promote the high-quality development of experimental animal technology and comparative medicine research in China. Table and Figures | Reference | Related Articles | Metrics

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A Preliminary Method for Continuous Drainage of Mesenteric Lymph Fluid in Rats Xiaorui ZHANG, Jing CAO, Qianqian WU, Kang KANG, Guoyuan CHEN, Baojin WU Laboratory Animal and Comparative Medicine    2022, 42 (4): 267-274.   DOI: 10.12300/j.issn.1674-5817.2022.024 Abstract （1359）   HTML （656）    PDF （2951KB）（1361）       Knowledge map    Save Objective To establish a novel sustained collection method for mesenteric lymph fluid by means of assisted reflux from the mesenteric-jugular lymphatic duct in rats. Methods Sixteen male Sprague-Dawley (SD) rats were randomly divided into two groups. The control group underwent duodenal and intestinal lymphatic duct cannulation, after which intestinal lymph fluid was collected. The experimental group underwent jugular vein and intestinal lymphatic duct cannulation to establish intestinal-jugular lymphatic duct assisted reflux. The intestinal lymph fluid was collected on the 7th day after the operation using an awake mobility device. The flow rate of intestinal lymph fluid was recorded, and its cellular components and some biochemical indicators were detected. Results Mesenteric-jugular lymphatic duct vein cannulation assisted reflux was successfully established in rats, and the rat models could be maintained for more than seven days. The intestinal lymph flow rate was （2.01±0.12） mL/h in the experimental group, which was higher than that of the control group [(0.92±0.09) mL/h, P＜0.01]. The number of lymphocytes (LYM#) and percentage of lymphocytes (LYM/%) in the experimental group were higher than those in the control group (P＜0.01). The percentage of neutrophils (NEUT/%) and percentage of monocytes (MONO/%) were lower than those in the control group (P＜0.01, P＜0.05, respectively). The concentrations of K+, Na+, CO2, and urea in the lymph fluid of the experimental group were higher than those of the control group (P＜0.01). However, the concentrations of triacylglycerol (TG) and P3+ were lower than those of the control group (P＜0.01). Conclusion This novel method can achieve real-time and long-term collection of mesenteric lymph fluid in rats under the condition of being awake, unrestricted in diet and in normal state, avoiding the influence of surgical stress, general anesthesia or animal restraint on the experimental results. Table and Figures | Reference | Related Articles | Metrics

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Advances in Animal Aging Models Danyang YIN, Yi HU, Rengfei SHI Laboratory Animal and Comparative Medicine    2023, 43 (2): 156-162.   DOI: 10.12300/j.issn.1674-5817.2022.094 Abstract （1292）   HTML （51）    PDF （751KB）（3008）       Knowledge map    Save With the increasing severity of global aging, aging-related issues have become the hotspot in the field of health. In recent years, animal aging models have been widely developed and applied, which is of great significance in the study of aging mechanism. Animals with short life span, such as Caenorhabditis Elegans and Drosophila Melanogaster, have natural advantages in the study of aging. Various rat and mouse aging models have been used in aging studies. In recent years, new animal aging models have been developed, such as the African turquoise killifish. The authors reviewed main animal models used in the study of aging, and analyzed the establishment methods, evaluation indexes, advantages and disadvantages of each model in order to provide reference for related research. Table and Figures | Reference | Related Articles | Metrics

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Research Progress of Tyzzer’s Organism in Quality Control of Laboratory Animals Junhao TAO, Huiqiong YAN, Hui XIE, Huazhong YING, Fangwei DAI Laboratory Animal and Comparative Medicine    2022, 42 (4): 358-363.   DOI: 10.12300/j.issn.1674-5817.2021.166 Abstract （1239）   HTML （647）    PDF （730KB）（1313）       Knowledge map    Save Tyzzer's organism is a kind of Clostridium piliforme, formerly Bacillus piliformis, which can cause hepatointestinal necrosis and diarrhea in animals. Tyzzer's disease caused by this pathogen is an acute disease with rapid onset, high mortality and no obvious clinical symptoms, so it is difficult to make early diagnosis and treatment. Once the outbreak, it will cause irreparable economic losses and laboratory safety problems. This article reviewed the biological characteristics, epidemiological and disease characteristics, detection methods, research progress of Tyzzer's organism, as well as the prevention and treatment of Tyzzer's organism. Reference | Related Articles | Metrics

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Research Progress in Animal Model of Alzheimer's Disease Zhejin SHENG, Limei LI Laboratory Animal and Comparative Medicine    2022, 42 (4): 342-350.   DOI: 10.12300/j.issn.1674-5817.2021.122 Abstract （1216）   HTML （379）    PDF （833KB）（3920）       Knowledge map    Save Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, which seriously affects the health of the elderly people. The drugs currently approved for the treatment of AD can only reduce the symptoms severity of AD, but can't cure AD or prevent the deterioration of AD. Over the past 40 years, there have been numerous treatments for AD, including compounds that prevent amyloid deposition in the brain or remove existing amyloid plaques, but their clinical curative effects are not significant. Therefore, more basic and clinical studies are needed to improve our understanding of the biological mechanism of AD. Experimental animal models are very important not only for the study of the pathogenesis of AD, but also for the development of AD drugs. This paper reviewed the main histopathological characteristics, genetic factors, the current animal models and model evaluation of AD. Table and Figures | Reference | Related Articles | Metrics

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History, Current Status, Challenges and Opportunities of Laboratory Monkey Industry in China SUN Qiang Laboratory Animal and Comparative Medicine    2024, 44 (4): 343-356.   DOI: 10.12300/j.issn.1674-5817.2024.112 Abstract （1161）   HTML （737）    PDF （1167KB）（2378）       Knowledge map    Save Laboratory animals play a crucial role in foundational scientific research and clinical medicine. Non-human primates (NHP), particularly Macaca mulatta and Macaca fascicularis, have long been highly valued due to their close resemblance to humans. After more than half a century of development, China's NHP laboratory animal industry has gradually transitioned from its early stage of rapid and unregulated growth to a mature stage of standardization and refinement. However, there has been a dramatic surge in global biopharmaceutical research in recent years, leading to a sharp increase in demand for NHP laboratory animals. This surge, coupled with the lack of long-term strategic planning among breeding enterprises, has resulted in severe aging of breeding populations and a significant decline in reproductive capabilities, further widening the supply gap. Under the dual pressures of rising demand and declining supply, the prices of NHP laboratory animals have surged. Although the cyclical downturn in the biopharmaceutical industry in recent years has lowered the demand for NHP laboratory animals to some extent, leading to significant price drops, the prices remain high. At the same time, against the backdrop of high prices, issues such as the accelerating aging of breeding populations, the lower standards for microbial quality control, insufficient genetic quality control, and blind investment in facility construction have emerged within the NHP laboratory animal industry. This report provides a comprehensive review of the history and current status of China's NHP laboratory animal industry, with a focus on laboratory monkeys. It explores the factors shaping the current industry landscape and identifies potential challenges and opportunities facing the industry. It aims to offer insights and references for the future development of China's NHP laboratory animal industry. Table and Figures | Reference | Related Articles | Metrics

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Research Progress on Establishing and Evaluation of Acne Animal Models Rui ZHANG, Meiyu LÜ, Jianjun ZHANG, Jinlian LIU, Yan CHEN, Zhiqiang HUANG, Yao LIU, Lanhua ZHOU Laboratory Animal and Comparative Medicine    2023, 43 (4): 398-405.   DOI: 10.12300/j.issn.1674-5817.2023.021 Abstract （1036）   HTML （50）    PDF （808KB）（2426）       Knowledge map    Save According to understanding of the pathogenesis of acne, scholars have established animal models of acne inflammation, animal models of grafting human skin acne, and natural acne animal models. The acne inflammation model is mainly induced by bacterial infection, chemical drug application, and foreign matter injection. Natural acne animal models include animals that some are sensitivity to hormones and some have clinical symptoms of acne. It is necessary to select appropriate model animals and replicate model methods for the development of acne intervention products with different degrees and mechanisms. At present, there are only human evaluation standards of acne health functions in China, but no animal evaluation standards, which has affected the in-depth study of the pathogenesis of acne as well as the research and development progress of acne products. This article summarizes the conditions for the occurrence of acne, the characteristics of human skin, the bidirectional effect of Cutibacterium acnes on human skin, acne animal models, and commonly used observation and evaluation indicators, providing the reference for studying the pathogenesis of acne, promoting acne treatment and health care, and developing treatment products. Table and Figures | Reference | Related Articles | Metrics

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Analysis of Common Types and Construction Elements of Diabetic Mouse Models Xue WANG, Yonghe HU Laboratory Animal and Comparative Medicine    2023, 43 (4): 415-421.   DOI: 10.12300/j.issn.1674-5817.2023.031 Abstract （1018）   HTML （58）    PDF （740KB）（1486）       Knowledge map    Save Diabetes mellitus is a disease characterized by absolute or relative lack of insulin, which leads to hyperglycemia, and its high mobidity and complications have a great impact on the lives of patients. Animal models are widely used to study the pathogenesis and treatment of diabetes and its complications. Different types of diabetes, with different pathogenesis and pathognomonic features, have different treatment options. In animal experimental, in addition to considering the genetic factors and physiological characteristics of the animal (such as sex and age), it is also necessary to consider the experimental protocol and various response options, which have a great impact on the experimental data, the reproducibility and stability of the experimental results. Therefore, it is necessary to select suitable animal models for experiments in the study of diabetes. Type 1 diabetes is characterized by absolute insulin deficiency, and existing mouse models of type 1 diabetes include chemically (STZ-induced) induced and spontaneous diabetes model (NOD mice), etc. Type 2 diabetes, characterized by insulin resistance and impaired glucose tolerance, is established in both obese and non-obese animal models, including diet-induced (high-fat diet induced), spontaneous diabetes (including monogenic and polygenic obese mice) models, and genetically modified mouse models. In this review, we discussed the common types of diabetic mouse models and analyzed the elements of their construction, the key factors that should be considered in the selection of diabetic mouse models, and explore the impact of these factors on the research of diabetes. Table and Figures | Reference | Related Articles | Metrics

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Overview of Studies in Animal Models of Schizophrenia Ling HU, Zhibin HU, Yunqing HU, Yuqiang DING Laboratory Animal and Comparative Medicine    2023, 43 (2): 145-155.   DOI: 10.12300/j.issn.1674-5817.2022.174 Abstract （1006）   HTML （59）    PDF （941KB）（3750）       Knowledge map    Save Schizophrenia (SCZ) is a highly destructive and complex psychiatric disorder illness, accompanied by a variety of positive and negative symptoms along with cognitive impairment, which brings a heavy social burden. Elucidation of the pathogenesis and therapeutic development is challenging because the complex interplay between genetic risk factors and environmental factors in essential neurodevelopmental processes. Therefore, preparing appropriate animal models can help people better understanding the neurobiological basis of SCZ and provide theoretical basis for finding new treatments. In order to provide reference for the application and improvement of SCZ animal models, this commentary reviewed several main modeling methods for animal models of SCZ, including neurodevelopmental models, drug-induced animal models, and genetic models, and the behavioral evaluation, histological analysis and possible molecular mechanisms of SCZ animal models were also outlined. Table and Figures | Reference | Related Articles | Metrics

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Introduction to the International Guide for Animal Research Reporting ARRIVE 2.0, and Its Implementation Plan in the Journal Junyan ZHANG, Xiaoyu LIU, Yao LI, Guoyuan CHEN, Xiao LU, Yu BAI, Xuancheng LU, Wanyong PANG, Baojin WU Laboratory Animal and Comparative Medicine    2023, 43 (1): 86-94.   DOI: 10.12300/j.issn.1674-5817.2023.014 Abstract （988）   HTML （86）    PDF （1381KB）（1693）       Knowledge map    Save Animal experiments play an important role in the process of biomedical research, and is a necessary way to transform basic medicine into clinical medicine. The standardization of animal experimental studies and reports determines the reliability and reproducibility of research results, and is also the key to transforming the results of animal experiments into clinical trials. In view of how to design and implement animal experiments, write animal experiment reports, and publish relevant academic papers in a more standardized way, LACM (Laboratory Animal and Comparative Medicine) has launched a new column of comparative medical research and reporting standards from 2023, focusing on the introduction and interpretation of international general norms related to laboratory animal and comparative medicine, such as ARRIVE 2.0 guidelines (Animal Research: Reporting of In Vivo Experiments). This article focuses on the development and application, basic content and priority of ARRIVE 2.0, as well as the scheme of implementing ARRIVE 2.0 guidelines in international biomedical journals, and explains the current situation and future plans of LACM following ARRIVE 2.0 guidelines. The research and report of animal experimental medicine following the ARRIVE 2.0 guidelines and other international norms is one of the important driving forces to promote the high-quality development of experimental animal science and biomedicine in China, and also a powerful means to implement the 3R principle and improve the welfare of laboratory animals. Through this article, we hope the majority of scientific researchers and editors will attach great importance and actively implement these international standards. Table and Figures | Reference | Related Articles | Metrics

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Literature Analysis of the Preparation Elements of Animal Models of Skin Photoaging and the Data of Subjects Yasheng DENG, Jiang LIN, Chiling GAN, Guanfeng ZENG, Jiayin HUANG, Huifang DENG, Yingxian MA, Siyin HAN Laboratory Animal and Comparative Medicine    2023, 43 (4): 406-414.   DOI: 10.12300/j.issn.1674-5817.2023.026 Abstract （984）   HTML （24）    PDF （805KB）（1104）       Knowledge map    Save Objective To analyze the modeling elements and subjects of the animal model of skin photoaging, and to provide a reference for the preparation and improvement of the model and a basis for the scientific evaluation of the subject. Methods By searching and collecting relevant literature on the preparation of animal models of skin photoaging from 2010 to 2022 in the China National Knowledge Infrastructure, Wanfang Database, and PubMed database, the model animal species, gender, modeling method, modeling cycle, radiation source and its distance from the modeling site, cumulative radiation volume, detection indicators, and subjects (drugs or treatments) recorded in the literature were collated and summarized, and a database was established for statistical analysis. Results 257 articles that met the inclusion criteria were selected. Among them, the most common animal model was SKH-1 hairless mice, followed by SD rats and KM mice; the gender of animals was mainly female, medium-wave ultraviolet B (UVB) was often used as the radiation source, the distance between the radiation source and the modelling site was mostly 30 cm, and the modelling period was usually 40-60 days. The cumulative dose of long-wave ultraviolet A (UVA) was between 100-150 J/cm2, and the cumulative dose of UVB was between 5-10 J/cm2. The tests used after model establishment were skin histopathological examination, skin tissue homogenization, fibre staining, immunoblotting, etc. Subjects included Chinese herbal medicines, Chinese herbal extracts, Chinese patent medicines, Chinese herbal compound medicines, chemical drugs, biological agents and other treatments, while the animal model of skin photoaging was also used for clinical efficacy studies of external Chinese medicine, physiotherapy and positive control drugs. Conclusion In skin photoaging animal experiments, female SKH-1 hairless mice are often used, and UVB is used as the radiation source. The modeling period is usually 40-60 days, and the minimum erythema dose (MED) is incremented week by week. The cumulative UVB irradiation dose ranges from 0 to 10 J/cm2, which has the advantages of high success rate, good reproducibility and high similarity with clinical disease. Table and Figures | Reference | Related Articles | Metrics

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Revision of Standards for Microbiological and Parasitological Grades in Laboratory Animals and Its Comparison to Foreign Standards Lianxiang GUO Laboratory Animal and Comparative Medicine    2023, 43 (4): 339-346.   DOI: 10.12300/j.issn.1674-5817.2023.088 Abstract （954）   HTML （100）    PDF （859KB）（3137）       Knowledge map    Save The national standard, GB 14922-2022 on "Laboratory Animal Microbiological and Parasitical standards and monitoring " was implemented on July 1st, 2023. This article is compiled according to the speech of the 16th East China Laboratory Annual meeting, explores and critically analyzes the developments made to the revised standard and examines how this framework compares with quality control programs of other established international institutions. The key aspects of establishing quality monitoring programs for animal-associated microorganisms in laboratory animal facilities are briefly discussed. Table and Figures | Reference | Related Articles | Metrics

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Explanation and Elaboration of the ARRIVE Guidelines 2.0—Reporting Animal Research and In Vivo Experiments (Ⅱ) Guoyuan CHEN, Xiao LU, Yu BAI, Lingzhi YU, Ying QIAO, Jian WANG, Jin LU, Xiaoyu LIU, Xuancheng LU, Jing GAO, Yao LI, Wanyong PANG Laboratory Animal and Comparative Medicine    2023, 43 (3): 323-331.   DOI: 10.12300/j.issn.1674-5817.2023.042 Abstract （897）   HTML （57）    PDF （1187KB）（3569）       Knowledge map    Save Improving the reproducibility of biomedical research results remains a major challenge. Transparent and accurate reporting of progress can help readers evaluate the reliability of research results and further explore an experiment by repeating or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is the second part of the Chinese translation of the complete interpretation of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (original text can be found at https://arriveguidelines.org ) and based on the best practices for following the ARRIVE 2.0 guidelines in international journals. This part includes Items 4-7 of "ARRIVE Essential 10" in the ARRIVE 2.0 guidelines: "Randomization", "Blinding", "Outcome Measurement", and "Statistical Methods". Our Chinese translated version aims to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhancing the standardization of experimental animal research and reporting, and promoting the high-quality development of experimental animal technology and comparative medicine research in China. Reference | Related Articles | Metrics

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Mechanism of Intermittent Fasting in Improving Olanzapine-induced Metabolic Disorders in Mice Han LI, Xiaorui ZHANG, Chengfang ZHANG Laboratory Animal and Comparative Medicine    2023, 43 (1): 3-10.   DOI: 10.12300/j.issn.1674-5817.2022.089 Abstract （892）   HTML （74）    PDF （2914KB）（903）       Knowledge map    Save Objective To explore the beneficial role and potential mechanism of intermittent fasting in olanzapine-induced metabolic disorders. Methods C57BL/6J mice were randomly divided into four groups: Saline + ad libitum (Saline+Ad libitum), Saline + intermittent fasting (Saline +IF), olanzapine administration + ad libitum (Olanzapine+ Ad libitum), and olanzapine administration + intermittent fasting (Olanzapine+IF)， with eight mice in each group. The IF group adopted the 5∶2 scheme, that is, fasting on Monday and Thursday every week, and eating freely in the rest of the time. Ad libitum feeding as the control of intermittent fasting, Saline gavage as the control of olanzapine administration. The experiment lasted for 12 weeks. The differences of body mass, liver mass and epididymal adipose tissue mass were compared between the olanzapine-treated group and the control group after IF intervention. The body fat mass, lean body mass, and visceral fat infiltration of mice were analyzed by nuclear magnetic resonance and HE staining, respectively. Furthermore, the levels of fasting blood glucose, insulin, and insulin resistance index (HOMA-IR) in the process of glucose metabolism were also measured by glucose oxidase method and radioimmunoassay, respectively. The effects of IF on H2O2 release and the level of cytochrome C mRNA, a marker related to mitochondrial damage, were detected by ELISA and real-time fluorescence quantitative PCR. Results After 12 weeks of treatment, olanzapine induced a significant increase in body mass, body fat, lean body mass and visceral fat infiltration (P<0.05), as well as fasting blood glucose, insulin, and HOMA-IR (P<0.05); however, IF significantly reduced the above indicators (P<0.05). Further studies showed that the release of H2O2 and the expression of Cytochrome C mRNA in adipose tissue of mice after intermittent fasting treatment were significantly decreased (P<0.05). Conclusion Intermittent fasting therapy can alleviate olanzapine-induced metabolic disorders in mice. The underlying mechanism may involve the inhibition of oxidative stress level and the maintenance of mitochondrial functions. Table and Figures | Reference | Related Articles | Metrics

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A Brief Interpretation of CCAC Guide on Humane Endpoints of Animals: 2022 Edition Xiaying LI, Yusheng WEI, Yonglu TIAN, Wanyong PANG Laboratory Animal and Comparative Medicine    2022, 42 (6): 566-571.   DOI: 10.12300/j.issn.1674-5817.2022.077 Abstract （892）   HTML （54）    PDF （987KB）（964）       Knowledge map    Save The 2022 Canadian Council On Animal Care (CCAC) guidelines: Identification of Scientific Endpoints, Human Intervention Points, and Cumulative Endpoints (CCAC Guide) supplements existing laboratory animal humane endpoint theory according to the latest available literature. This article summarized the main content of the 2022 CCAC Guide, and elaborated and analyzed the determination, implementation and supervision of the scientific endpoints, humane intervention points, and cumulative endpoints of animal experiments, in order to provide useful reference and information. Table and Figures | Reference | Related Articles | Metrics

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Practice of ABSL-2 Laboratory Process Management in Universities： Xiamen University as An Example Xiuqing ZHENG, Zhiqiang SHAO, Jing SONG, Yuehua ZHANG, Jinhua SU Laboratory Animal and Comparative Medicine    2022, 42 (4): 364-370.   DOI: 10.12300/j.issn.1674-5817.2021.160 Abstract （842）   HTML （367）    PDF （1300KB）（1008）       Knowledge map    Save The establishment of standardized, scientific and normalized animal biosafety level-2 (ABSL-2) laboratory is an important supporting of teaching and research in universities. Taking the ABSL-2 laboratory of Xiamen University laboratory animal center as an example, this paper elaborated the operation and management mode of the ABSL-2 laboratory from the aspects of the qualification for the record, biosafety management system documents, daily work management, pressure gradient control, the management of people, animals and materials, biological safety supervision and inspection, and waste disposal, and proposed countermeasures for the problems encountered in the management process. Table and Figures | Reference | Related Articles | Metrics

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Three Dimensions of Animal Experiment Ethics: Analysis Based on Value of Life, Animal Welfare, and Risk Prevention ZHAO Yong Laboratory Animal and Comparative Medicine    2024, 44 (4): 445-454.   DOI: 10.12300/j.issn.1674-5817.2024.108 Abstract （832）   HTML （60）    PDF （1033KB）（2484）       Knowledge map    Save Ethical review of animal experiments is based on factors such as the necessity of the experiment, its scientific validity, the professional competence of the experimenters, and research conditions, to determine the ethical permissibility of an animal experiment. Attitudes towards laboratory animals and animal experiments vary significantly due to differences in cultural traditions, religious beliefs, personality traits, and roles within the experimentation process. How animal experiment ethics can advance in tandem with the advancements of life sciences, while consistently providing forward-looking guidance and safeguarding fundamental ethics, is a subject that requires continuous exploration, practice, and research. Ensuring the welfare of laboratory animals has now become a widely accepted ethical consensus. However, attitudes and principles towards different types of animal experiments, and the methods to genuinely and effectively ensure the welfare quality of animals during live animal experiments, should be central to animal experiment ethics. Based on the deep integration of biotechnology in the field of laboratory animals, this paper considers the contribution of animal experimentation to the development of scientific ethical concepts. It systematically elucidates the special value of life in laboratory animals and their relationship with biosafety and ecological safety. It also outlines welfare quality assessment methods for different species of laboratory animals, demonstrating that the philosophical ideology of the value of life is the core of animal experiment ethics. The quality and significance of animal experiments determine the ethical level at which the value of life in laboratory animals is realized, and animal welfare technologies provide a robust ethical guarantee for animal experiments. The close integration of ethical theories with life sciences in laboratory animals is an objective requirement for animal experiment ethics. The value of life, animal welfare, and risk prevention collectively form the core elements of ethical review in animal experiments, serving as fundamental factors in improving the quality of ethical reviews and avoiding ethical deviations. Reference | Related Articles | Metrics

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Preliminary Study on Raising and Maintaining Clean Mice with Micro-barrier Cages in Conventional Environmental Facilities Qi REN, Yandong LI, Qiang SUN Laboratory Animal and Comparative Medicine    2022, 42 (5): 440-447.   DOI: 10.12300/j.issn.1674-5817.2022.129 Abstract （824）   HTML （67）    PDF （1562KB）（1975）       Knowledge map    Save Objective To explore the feasibility of breeding cleaning degree mice with micro-barrier cages in conventional environmental facilities. Methods Clean-grade mice were housed and maintained in positive-pressure microbarrier cages in a general environment, during which third-party sampling of the microbial status of the animals in the microbarrier was performed on a quarterly frequency. Results From June 2020 to July 2022, no microorganisms that must be excluded by the national standard for cleaning degree mice have been detected in two consecutive years. Conclusion Micro-barrier cages can be used to raise and maintain cleaning grade mice in conventional environmental facilities. Table and Figures | Reference | Related Articles | Metrics

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Advances and Challenges in the Research of Integration Methods of Animal Experimental Evidence ZHENG Qingyong, LI Tengfei, XU Jianguo, ZHOU Yongjia, MA Zhichao, WANG Na, LI Molan, YANG Wenjing, WU Peirun, WANG Haidong, TIAN Jinhui Laboratory Animal and Comparative Medicine    2024, 44 (5): 567-576.   DOI: 10.12300/j.issn.1674-5817.2024.079 Abstract （806）   HTML （26）    PDF （1365KB）（952）       Knowledge map    Save Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health. Table and Figures | Reference | Related Articles | Metrics

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Establishment and Evaluation of a Moderate-to-Severe Knee Osteoarthritis Model in Rats Induced by Surgery SUN Xiaorong, SU Dan, GUI Wenjuan, CHEN Yue Laboratory Animal and Comparative Medicine    2024, 44 (6): 597-604.   DOI: 10.12300/j.issn.1674-5817.2024.066 Abstract （801）   HTML （232）    PDF （1789KB）（530）       Knowledge map    Save Objective To establish a rat model of moderate-to-severe knee osteoarthritis, laying the foundation for studying the pathogenesis of moderate-to-severe knee osteoarthritis and its prevention and treatment methods. Methods Thirty male SD rats were randomly divided into three groups: a sham surgery group, an 8-week model group, and a 20-week model group, with 10 rats in each group. Rats in the 8-week and 20-week model groups underwent surgery to cut the anterior and posterior cruciate ligaments and medial collateral ligament of the right knee joint, and remove the medial and lateral menisci. After surgery, the rats were allowed to move freely. The rats in the sham surgery group had only skin incisions to expose the joint without any surgical treatment. At 8 and 20 weeks post-surgery, Micro-CT scans were performed to analyze the femoral osteoporosis in the rats. After euthanizing the rats, gross observations of the knee joints were made, and the cartilage of the joint surface was scored using the Pelletier scoring system. The knee joints were collected for hematoxylin and eosin (HE) staining and safranin O-fast green staining to observe changes in cartilage morphology. The modified Mankin's scoring system was used to assess the tissue pathology of the joint surface. Immunohistochemical staining was used to detect the expression of type II collagen and matrix metalloproteinase 13 (MMP13), reflecting the anabolic and catabolic metabolism of the knee joint cartilage. Results The knee joint cartilage in the 8-week and 20-week model groups was severely damaged, with Pelletier and modified Mankin's scores significantly higher than those in the sham surgery group (both P<0.01). The Pelletier and modified Mankin's scores in the 20-week model group were significantly higher than those in the 8-week model group (P<0.01). Micro-CT observations revealed irregular joint surfaces, osteophyte formation, and signs of osteoporosis in both the 8-week and 20-week model groups, with the 20-week model group showing more loose bodies around the knee joints. Immunohistochemical staining showed increased expression of MMP13 and decreased expression of type II collagen in the knee joint tissues of the model groups, indicating that the balance of anabolic and catabolic metabolism in the joint cartilage was disrupted. MMP13 increased while type II collagen decreased. Conclusion The surgical method of cutting the anterior and posterior cruciate ligaments and medial collateral ligament and removing the medial and lateral menisci successfully creates a moderate-to-severe knee osteoarthritis model in rats. Imaging examinations reveal osteophytes, osteoporosis, and loose bodies in the knee joints, while pathological observations show a reduction or even disappearance of joint cartilage, with a disruption in the balance of cartilage anabolic and catabolic metabolism. Table and Figures | Reference | Related Articles | Metrics

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Investigation on Biological Characteristics and Aging Phenotype of SHJH hr Mice Huiqing TANG, Shufu CHANG, Zhifeng YU, Lei ZHANG, Xiaoqian TAN, Wei QU, Liang LI, Zhen QIAN, Jianzhong GU, Ping XU Laboratory Animal and Comparative Medicine    2023, 43 (1): 44-52.   DOI: 10.12300/j.issn.1674-5817.2022.069 Abstract （795）   HTML （38）    PDF （2106KB）（1102）       Knowledge map    Save Objective To measure and analyze biological characteristics and aging phenotype of SHJH hr mice and provide basic data for the application of the mouse model in aging mechanisms research and antiaging drug development. Methods With ICR mice of the same age as control group, the body mass growth data of SHJH hr mice at the age of 3 to 16 weeks, the reproduction ability of 1 to 4 fetuses and the life cycle of SHJH hr mice were measured. Blood routine (30 items) and serum biochemical indexes (25 items) of 6-week-old SHJH hr mice were measured. The venous blood of 8-week-old SHJH hr mice was collected for flow cytometry analysis to determine the content of immune cells. The aging bone structure of the cancellous bone and bone mineral density of SHJH hr mice aged 4, 8 and 26 weeks were measured by micro-CT. Histopathological changes of bone and joint of 8-week-old mice were observed. Results Compared with ICR mice, the female and male body mass of SHJH hr mice were significantly lower at the age of 16 weeks (P < 0.05), and the reproductive performance of female mice was low (P < 0.01) or did not have normal reproductive capacity. The shortest survival time of SHJH hr mice was 57 weeks and the longest was 71 weeks, which was shorter than those of normal ICR mice, showing obvious rapid aging phenomenon. At the same time, some physiological and biochemical indexes of blood and pathological changes of bone and cartilage tissues also showed the accelerated aging and abnormality of animal physiological functions. Conclusion SHJH hr mice have some biological characteristics of rapid aging as well as some physiological and pathological changes caused by aging. Table and Figures | Reference | Related Articles | Metrics

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Histological Characteristics of the Kidney in Mongolian Gerbils of Different Ages Lingqun LU, Honggang GUO, Qiaojuan SHI, Fangwei DAI, Xiaofeng CHU Laboratory Animal and Comparative Medicine    2023, 43 (1): 61-66.   DOI: 10.12300/j.issn.1674-5817.2022.130 Abstract （780）   HTML （23）    PDF （1354KB）（1308）       Knowledge map    Save Objective To explore the histological characteristics of the kidney in Mongolian gerbils of different ages. Methods Ten Mongolian gerbils of 2, 6, and 12 months old (half male and half female) were selected. After euthanasia, the kidneys were taken and paraffin sections were made. After HE, MASSON and PAS staining, the structural differences of different parts of the kidney tissue in gerbils of different ages were observed by digital scanning, and the relevant data of the kidney tissue were measured by image analysis software. Results The number of proximal convoluted tubules was more than that of distal convoluted tubules in the renal cortex and outer medulla of gerbils. With age, the glomerular density decreased, the glomerular diameter increased, the basement membrane of renal tubules thickened, and the fibrous components between renal tubules increased. Conclusion The histological structure of Mongolian gerbil's kidney varies with age, which may be related to glomerulosclerosis and parenchymal cell reduction. The specific mechanism needs further study. Table and Figures | Reference | Related Articles | Metrics

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Guidelines for the Selection of Animal Models and Preclinical Drug Trials for Spontaneous Intracerebral Hemorrhage (2024 Edition) Committee of Experts on Medical Animal Experiments, Chinese Research Hospital Association Laboratory Animal and Comparative Medicine    2024, 44 (1): 3-30.   DOI: 10.12300/j.issn.1674-5817.2024.001 Abstract （776）   HTML （249）    PDF （1252KB）（2163）       Knowledge map    Save Spontaneous intracerebral hemorrhage (sICH), the most prevalent and lethal subtype of stroke, is characterized by spontaneous hemorrhage in the brain parenchyma. Presently, there are no effective methods for preventing and treating sICH. The existing sICH animal models can be broadly categorized into three classes: (1) induced intracerebral hemorrhage models, including autologous blood injection model, collagenase injection model, microballoon inflation model, and hyperglycemia-induced sICH hematoma expansion model; (2) spontaneous hypertensive intracerebral hemorrhage models mainly include stroke-prone spontaneously hypertensive rats (SHRsp) and stroke-prone renovascular hypertensive rats (RHRsp); (3) gene-modified models encompassing transgenic hypertensive intracerebral hemorrhage, transgenic cerebral amyloid angiopathy, arteriovenous malformation-related, cerebral cavernous malformation-related and collagen-related genetically modified animal models for sICH. These models contribute not only to unraveling the pathogenesis of sICH and exploring preventive or therapeutic interventions, but also serve as invaluable tools for conducting preclinical drug trials to advance novel treatments. This guide comprehensively reviews sICH pathogenesis, delineates the superiority and inferiority of different species of modeling animals, explains the modeling principles and techniques for various sICH animal models, elucidates the technical details of animal model production, summarizes the pathophysiological mechanism simulated by the models and their clinical relevance, outlines the neurobehavioral evaluation methodologies for sICH animal models, compares the advantages and disadvantages of various models, and suggests their applicable research areas. Additionally, it underscores critical considerations in the design of preclinical drug trials for sICH. Table and Figures | Reference | Related Articles | Metrics

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Establishment of PCR Identification Method for Pig Blood Type Jiaoxiang WANG, Yan WANG, Ke HU, Kaixiang XU, Taiyun WEI, Deling JIAO, Heng ZHAO, Hongye ZHAO, HongJiang WEI Laboratory Animal and Comparative Medicine    2023, 43 (6): 585-594.   DOI: 10.12300/j.issn.1674-5817.2023.065 Abstract （773）   HTML （454）    PDF （2710KB）（806）       Knowledge map    Save Objective Xenotransplantation is an effective way to address the shortage of human organ donors, but it faces serious immune rejection reactions, including hyperacute rejection caused by blood type differences. Establishing a stable, convenient, and reliable method for pig blood type identification can quickly screen suitable donor pigs for xenograft research. Methods Banna miniature inbred pigs, Diannan small eared pigs, and Bama Xiang pigs were selected as the research objects. DNA was extracted from the blood, oral buccal mucosa, and fetal fibroblasts of the three strains of pigs using DNA extraction kits. The target fragment of the ABO homologous gene EAA intron 7 in pigs was amplified using PCR method. Blood agglutination reaction was used to detect hemolysis in pig anterior vena cava whole blood after adding anti A and B antibodies. Immunohistochemical method was used to detect the expression level of A antigen in pig heart, liver, spleen, lung, and kidney tissues. Immunofluorescence method was used to detect the expression level of A antigen in pig oral mucosa. By comparing the results of different methods for determining pig blood types, the stability and reliability of the PCR method were verified, and a convenient PCR based pig blood type identification method was established. Results Firstly, the blood PCR results of 69 inbred strains of Banna miniature pigs, 7 Diannan small eared pigs, and 34 Bama Xiang pigs showed 20 AO blood types, 66 AA blood types, and 24 O blood types. The PCR results of fetal fibroblasts from 47 Diannan small eared pigs showed that all 47 fetuses were O blood type. Among them, the oral mucosal PCR results of 8 gene edited cloned pigs were consistent with those of donor fetal fibroblasts, all of which were O blood type. The oral mucosal PCR results of 8 wild-type pigs (2 inbred lines of Banna miniature pigs, 4 Diannan small eared pigs, and 2 Bama Xiang pigs) were consistent with the blood PCR identification results. Then, 11 inbred lines of Banna miniature pigs, 4 Diannan small eared pigs, and 2 Bama Xiang pigs were randomly selected for blood agglutination reaction validation, and the results were consistent with the PCR identification results of both blood samples and oral mucosa samples. Moreover, immuno-histochemical analysis was performed on the heart, liver, lung, kidney, and spleen tissues of one Banna miniature pig inbred line and two Bama Xiang pigs, and the results were consistent with blood PCR identification and blood agglutination reaction results. Finally, oral mucosal samples were collected from 2 inbred strains of Banna miniature pigs and 1 Bama Xiang pig for immunofluorescence detection, and the results were consistent with the blood PCR identification results. Conclusion By collecting fetal cells and oral mucosal samples from live pigs for PCR detection, the blood type of pigs can be accurately and efficiently identified, providing a convenient method for blood type screening of xenograft donor pigs. Table and Figures | Reference | Related Articles | Metrics

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H1 Linker Histone Gene Regulates Lifespan via Dietary Restriction Pathways in Caenorhabditis elegans Hui CHENG, Fei FANG, Jiahao SHI, Hua YANG, Mengjie ZHANG, Ping YANG, Jian FEI Laboratory Animal and Comparative Medicine    2023, 43 (3): 271-281.   DOI: 10.12300/j.issn.1674-5817.2022.183 Abstract （754）   HTML （33）    PDF （1521KB）（1526）       Knowledge map    Save Objective To reveal the physiological function of H1 linker histone gene (hil-1) and its molecular mechanism for regulating the lifespan in Caenorhabditis elegans (C. elegans). Methods C. elegans was used as a model organism and hil-1 gene was knock-down, knock-out and over-expressed via RNA interference technology, hil-1(gk229) mutants backcross purification and microinjection technology. Then the survival and oviposition of C. elegans were observed. Physiological tests including heat shock test, paraquat stress test and heavy metal Cr6+ stress test were conducted to evaluate the stress resistance of hil-1 mutants. After constructing a dual mutant nematode, real-time fluorescence quantitative PCR (RT-qPCR) was used to further identify the signaling pathways and target sites associated with hil-1 gene regulatory lifespan. Results Compared with wild-type N2 worms, the lifespan of C. elegans of RNA interference and hil-1(gk229) mutants were significantly shortened (P<0.001), while overexpression of hil-1 in the whole body increased lifespan (P<0.05). The tolerance of hil-1(gk229) mutants to heat stress and oxidative stress was significantly decreased (P<0.001, P<0.05), but the tolerance to heavy metals was not different compared to wild-type N2 worms (P>0.05). In addition, the developmental cycle of hil-1(gk229) mutants was shortened and the time of oviposition was advanced (P<0.001), but there was no significant change in total number of oviposition (P>0.05). After feeding hil-1 RNA interference bacteria to eat-2(ad465) mutants, the down-regulation of hil-1 expression did not affect the lifespan of eat-2(ad465) mutants (P>0.05). Compared with wild-type N2 worms, the expression level of daf-16 in hil-1(gk229) mutants was significantly down-regulated (P<0.001), and the expressions of downstream genes, mtl-1 and ctl-1, were also down-regulated (P<0.05, P<0.001). Compared with daf-2(e1370) mutants, the lifespan of daf-2 (e1370); hil-1(gk229) mutants did not shortened (P>0.05). Compared with daf-16(mu86) mutants, the lifespan of daf-16(mu86); hil-1(gk229) mutants was significantly shortened (P<0.001). The knockdown of hil-1 via RNA interference technology, specifically in epidermis and intestine, was sufficient for lifespan reduction (P<0.001). Conclusion The deletion of hil-1 gene significantly shortened the lifespan of C. elegans and decreased the tolerance to heat and oxidative stress. The hil-1 gene regulates the lifespan of C. elegans via dietary restriction pathway and acts mostly in epidermis and intestine. Table and Figures | Reference | Related Articles | Metrics

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Evaluation of Pain in Acute Pulpitis Hyperalgesia Model Rats Sijia ZHAO, Xinyu HE, Quan JING, Lin MA, Chunlan GUO, Kuo WAN Laboratory Animal and Comparative Medicine    2022, 42 (4): 333-341.   DOI: 10.12300/j.issn.1674-5817.2021.171 Abstract （754）   HTML （368）    PDF （1551KB）（2311）       Knowledge map    Save Objective To establish a rat hyperalgesia model of acute pulpitis induced by lipopoly-saccharide (LPS) administration to the maxillary molars. In addition, to analyze and evaluate the acute pain and LPS-induced pulpitis, and to investigate the change of pain threshold in rats with acute pulpitis. Methods Forty-five adult male Sprague-Dawley (SD) rats were equally divided into LPS group, normal saline (NS) group, and blank control (SHAM) group, with 15 rats in each group. Under isoflurance anesthesia, the rats in the LPS group had their right upper molar teeth drilled and LPS was sealed temporarily with Caviton, while those in the NS group had their right upper molar teeth drilled and normal saline was sealed temporarily with Caviton. Rats in the SHAM group, serving as blank control group,were only anesthetized with isoflurane. Pain behavioral indexes, including spontaneous pain behavior scores, 50% paw withdrawal threshold (PWT), head withdrawal thresholds (HWT), paw withdrawal latency (PWL), and head withdrawal latency (HWL) were measured before and 2 h, 24 h, 48 h, and 72 h after surgery. After rats were anesthetized and sacrificed, the pathological status of pulp tissues was confirmed with hematoxylin-eosin staining and pathological examination and serum IL-1β and TNF-α were determined by ELISA. Results Concerning spontaneous pain behavior, the facial grooming time in the LPS group was significantly higher than that in the NS group postoperatively (P＜0.05), and increased gradually with time, although there was no significant difference in activity time. The HWT in the LPS group was significantly lower than that in the NS group at 2 h, 24 h, and 48 h postoperatively (P＜0.05). Additionally, 50% PWT in the LPS and NS groups were significantly lower than those in the SHAM group (P＜0.05). The LPS group had a significantly lower HWL than the NA group at 2 h and 48 h postoperatively (P＜0.05). Likewise, the PWL was significantly lower in the LPS group than the NS group (P＜0.05) at 72 h postoperatively. The IL-1β and TNF-α levels in the rats’ serum were significantly higher in the LPS group than in the NS group (P＜0.01 or P＜0.05). Moreover, the IL-1β and TNF-α levels in all groups began increasing 2 h after the model establishment, reaching a peak at 48 h. The pathological results of the LPS group showed a gradual expansion in the neutrophil infiltration area from the point of perforation to the crown pulp and upper root pulp, in 24-72 h after modeling. The rats in the NS group exhibited milder degree of inflammation than those in the LPS group. Conclusion Based on the observations regarding rat behavior, pathological changes of dental pulp, and detection of inflammatory factors in serum, the LPS induced acute pulpitis model causes pathological pain and pain threshold alterations in rats. Table and Figures | Reference | Related Articles | Metrics

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Modified Method for Inducing Acute Intestinal Fibrosis in Rats Using 2,4,6-Trinitrobenzene Sulfonic Acid Yiru WANG, Xiaoying JIANG, Ruoxi DONG, Yibin PAN, Xianghui HAN, Yongqing CAO Laboratory Animal and Comparative Medicine    2022, 42 (4): 284-293.   DOI: 10.12300/j.issn.1674-5817.2021.147 Abstract （751）   HTML （866）    PDF （2735KB）（1225）       Knowledge map    Save Objective To explore 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute intestinal fibrosis in rats and the effect of different drug ratios. Methods Thirty female Sprague-Dawley (SD) rats were randomly divided into five groups with six rats in each group. Groups A to D were the model groups, in which the rats were induced by modified retention enemas using solutions with different drug ratios: group A, 5% TNBS + 50% ethanol (1∶1 v/v); group B, 5% TNBS + 75% ethanol (1∶1 v/v); group C, 5% TNBS + 100% ethanol (1∶1 v/v); group D, 5% TNBS + 50% ethanol (2∶1 v/v); and the control group was induced by normal saline (0.9% sodium chloride solution) enema. The symptoms, signs, and body mass changes of the animals were observed within one week after modeling, and scored using the disease activity index (DAI). At 7th d and 14th d after model establishment, half of the rats in each group were randomly selected for sampling to observe the degree of gross damage to the colon tissue and scored using the colon macroscopic damage index (CMDI). Pathological sections of colon tissue were stained with hematoxylin-eosin (HE) to observe the severity of enteritis, and Masson staining was used to observe collagen fiber deposition. Results The rats in each model group showed enteritis and intestinal fibrosis lesions of different severities, of which 5% TNBS + 75% ethanol solution (1∶1 v/v) did not lead to death during the observation period. At 24 h after model establishment, the rats had significantly decreased body weight, loose stool, and bloody stool, significant colonic wall fibrosis lesions, and increased DAI and CDMI scores compared with the control group (P＜0.05). The degree of inflammation was transmural and more severe, as seen under the light microscope, and Masson staining showed that the intestinal wall at the model site was significantly thickened, and diffuse collagen fiber deposition occurred in the submucosa, muscular layer, and serosal layer. Conclusion The modified TNBS retention enema method can effectively construct a rat model of intestinal fibrosis, and the model established using 5% TNBS + 75% ethanol solution (1∶1 v/v) can simulate the two major characteristics of Crohn’s disease fibrosis, namely transmural inflammation and intestinal wall fibrosis. This method is simple and efficient, and the mortality rate of animals is low. Table and Figures | Reference | Related Articles | Metrics

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Genetic Characteristics and Research Progress of Feline Coronavirus TAO Lingyun Laboratory Animal and Comparative Medicine    2024, 44 (6): 661-666.   DOI: 10.12300/j.issn.1674-5817.2024.069 Abstract （750）   HTML （25）    PDF （734KB）（474）       Knowledge map    Save Feline coronavirus (FCoV) is classified into two biotypes: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). FIPV and FECV might evolve and mutate via genetic recombination and mutation, leading to novel subtypes and variants. This study examined the genomic structure and biological subtyping of FCoV, analyzed the infection characteristics of FIPV and FECV, and investigated the mechanisms of FECV transforming into FIPV. The findings revealed that while their genome structures were fundamentally similar, differences in their ability to efficiently infect monocytes/macrophages significantly influenced their pathogenicity and transmission characteristics, with FIPV exhibiting higher virulence. Moreover, the analysis of the open reading frames (ORF)3/7 as well as the N/S sequences of FIPV indicated that its non-structural proteins were associated with modulation of the host immune system. These proteins enabled immune evasion, leading to more severe disease. The genomic variability of FCoV constitutes an important foundation for studying the pathogenicity and epidemiology of FIPV and FECV, and offers references for virus detection and drug development. Reference | Related Articles | Metrics

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Statistical Analysis of the Leakage Situation in the Automated Watering System for Mice in Tsinghua University Laboratory Animal Resources Center Qianqian TANG, Xiuli ZHANG, Zai CHANG Laboratory Animal and Comparative Medicine    2024, 44 (1): 85-91.   DOI: 10.12300/j.issn.1674-5817.2023.132 Abstract （748）   HTML （69）    PDF （1306KB）（670）       Knowledge map    Save Objective To calculate the leakage rate of the automated watering system in Tsinghua University Laboratory Animal Resources Center, to evaluate the safety of the system, and provide references for selection, maintenance, and management of automated watering systems in animal facilities. Methods This study investigated the automated watering system installed in South and North Barriers of Tsinghua University Laboratory Animal Resources Center (Phase II). Water leakage monitoring was conducted over two periods, one over a period of 3 years and the other over 1.5 years. The occurrence of water leakage events at the two barriers during the monitoring period was statistically analyzed, classifying the causes into four categories: mishandling by personnel, animal behavior, obstruction by foreign objects, and deformation of fittings. The total daily leakage rate due to these causes and the daily leakage rate caused by quality issues, i.e. obstruction by foreign objects and deformation of fittings were calculated. Further analysis and discussion focused on the causes of water leakage and its impact on the facilities. At the same time, the number of caretakers at the end of the monitoring period in the Phase I facility without automated watering system and the Phase II facility with automated watering system were counted. Finally the difference in the number of cages per capita under the two watering systems was calculated. Results A total of 52 water leakage incidents occurred in both areas during the monitoring period, with a total daily leakage rate of 0.000 13%. Among them, 31 were caused by personnel mishandling, accounting for approximately 60% of total leakages. Enhanced training, supervision, inspection, and effective reminder measures could reduce leakage caused by personnel mishandling. There were 2 cases of water leakages caused by animal behavior, 0 leakage due to obstruction by foreign objects, and 19 leakages due to system quality issues, with a daily leakage rate of 0.000 07%. According to the operation data of Tsinghua University Laboratory Animal Resources Center, the average number of cages managed per person in facilities equipped with the automated watering system was 908, compared to 570 cages in facilities without the automated watering system. This represents an approximate 59% increase in the number of cages managed per person with the adoption of the automated watering system. Conclusion The daily leakage rate of the automated watering system in the Tsinghua University Laboratory Animal Resources Center is significantly lower than the theoretical design rate of 0.003%, which demonstrates the system's safety and effectiveness. Additionally, the adoption of an automated watering system can signi?cantly enhance caretaking ef?ciency. While initial investments in the system are required, the subsequent increase in ef?ciency leads to a continuous decrease in labor costs, thereby reducing the total operational expenses of the facility. In the context of modernizing animal facility construction, automated watering systems are becoming an essential consideration in facility design and operation. Table and Figures | Reference | Related Articles | Metrics

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Fine Structure of the Trunk Kidney and Distribution of Its Secreted Exosomes in the Adult Zebrafish Jinxing LIN, Xindong WANG, Xuebing BAI, Liping FENG, Shuwu XIE, Qiusheng CHEN Laboratory Animal and Comparative Medicine    2023, 43 (5): 531-540.   DOI: 10.12300/j.issn.1674-5817.2023.070 Abstract （726）   HTML （136）    PDF （3115KB）（3601）       Knowledge map    Save Objective To observe the fine structure of the trunk kidney in zebrafish, and to identify its secreted exosomes. Methods The microstructure and ultrastructure of the trunk kidney in zebrafish were observed by light microscopy and electron microscopy, and the particle size of exosomes was detected by nanoparticle tracking analysis (NTA). Results The trunk kidney was close and parallel to the spine in adult zebrafish. The nephron consisted of renal tubules and renal corpuscles. The renal tubules could be further divided into three types: proximal convoluted tubules, distal convoluted tubules, and cervical segments. The renal corpuscles were composed of glomerulus and renal capsules. The periodic acid-Schiff (PAS) staining results revealed that there were abundant glycogen granules in the proximal convoluted tubules, with brush-like outline in the apical surface of epithelial cells. Under transmission electron microscopy (TEM), there were exosomes distributed in the lumen of renal tubules, with numerous late endosomes and few number of multivesicular bodies (MVBs) in the cytoplasm of the epithelial cells concentrating on the apical side. Meanwhile, MVBs were also distributed in the apical regions of the renal tubules and the podocytes of the renal glomeruli. Immunohistochemical staining results showed that CD9, CD63 and TSG101 were strongly expressed in the lumen surface of the renal tubules, but weakly expressed in the corpuscles and lumen. NTA and TEM results showed that the exosomes isolated from zebrafish trunk kidney were saucer-like outline, and the particle size mode was 144.4 nm, which was consistent with the characteristics of morphological futures of exosome. Conclusion The zebrafish somatic kidney has the typical structure of the mammalian kidney and is the urinary organ in the body. The renal tubules have the ability to secrete exosomes, and their formation is a process of releasing poly-vesicles to the free surface of epithelial cells into the extracellular space. This study laid a morphological foundation for further study of exosomes in urinary function in aquatic experimental animals as well as the development and application of related models. Table and Figures | Reference | Related Articles | Metrics

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A Preliminary Study on the Domestication and Breeding Methods of Experimental Cats Yongping HE, Meixian XIE, Zhihui PANG, Qingxiu LI, Huahong HE, Namin ZHANG, Wei LI Laboratory Animal and Comparative Medicine    2023, 43 (1): 67-72.   DOI: 10.12300/j.issn.1674-5817.2022.118 Abstract （722）   HTML （30）    PDF （953KB）（1750）       Knowledge map    Save Objective Focused on the laboratory animal domestication and breeding of domestic cats, to explore the feeding management methods and breeding techniques of experimental cats. Methods Seven Chinese garden cats from three litters were introduced from the rural suburbs of Guangzhou, and a breeding seed colony was established. The cats were domesticated in captivity, bred, closed breeding and transmission according to the feeding and management methods of laboratory animal. The population reproduction, the number of pregnancies per year, the litter season, the birth and weaning quality of the cats, and the survival rate of weaning were statistically collected. Results The young breeding cats were able to adapt to the cage feeding management. In the transmission breeding and the expanded breeding colony, the number of female cats pregnant with one, two or three litters a year accounted for 63.2%, 26.3% and 10.5%, respectively. The proportions of litters born from the 1st to the 4th quarters were 20.7%, 20.7%, 27.6%, and 31.0%. A total of 29 pregnancies and 101 kittens were got from 19 female cats, with an average of (3.5±1.33) kittens per litter. The birth weights of female and male cats were (89.31±13.69) g and (93.47±15.12) g, respectively. Sixty-seven kittens survived from weaning. The average survival rate was 60.86%, and the weaning weights of female and male cats were (361.62±82.77) g and (376.0±91.71) g, respectively. Conclusion Domestic Chinese garden cats can adapt to laboratory animal feeding and breeding rules, and have strong fertility. They can normally pregnant and breeding throughout the year. The kittens grow to 5-6 months of age can meet the weight requirements for the examination of pharmaceutical hypotensive substances, and can be used as experimental cats for pharmaceutical examination with clear origin. Table and Figures | Reference | Related Articles | Metrics

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Effects of Bevacizumab Injection on the Skin Wound Healing in Cynomolgus Monkeys Ping YANG, Li CUI, Cheng YU, Zhiyue WEN Laboratory Animal and Comparative Medicine    2023, 43 (1): 21-29.   DOI: 10.12300/j.issn.1674-5817.2022.128 Abstract （716）   HTML （27）    PDF （2018KB）（1421）       Knowledge map    Save Objective By observing the impact of Bevacizumab injection on the speed of wound healing and the expression of CD34 in cynomolgus monkeys, to verify its delayed wound healing mechanism, and to provide clinical reference for the dosage and frequency of Bevacizumab treatment for oncology surgery patients. Methods Six male cynomolgus monkeys underwent full-thickness skin resection on the back to establish a wound healing evaluation model. Three cynomolgus monkeys were randomly selected as the saline group, and the other three cynomolgus monkeys were allocated to the Bevacizumab treatment group. The monkeys of Bevacizumab group were administrated with Bevacizumab injection (30 mg/kg, i.v.) on day 0, day 4, day 8, and day 11, respectively. The monkeys of saline group were injected with the same volume of saline as the group receiving Bevacizumab. The blood routine test was conducted, and the wound healing of each group of cynomolgus monkeys was observed 28 days after operation. The wound healing rate was analyzed by software Image J, and the severity of the wound was assessed by scoring method. Wound healing skin samples of 6 cynomolgus monkeys were obtained after 4 weeks, and the expression level of CD34 in the wound skin tissues was detected using immunohistochemistry. Results A skin excision wound model has already been established in cynomolgus monkeys. The number of white blood cells and neutrophils in the blood of cynomolgus monkeys increased significantly on the 3rd day after operation (P<0.05), and the number of white blood cells gradually returned to normal on the 7th day, while the number of red blood cells, hemoglobin and hematocrit did not change significantly, suggesting that the animals were in good nutritional status. The Bevacizumab injection group wound healing rate was significantly slower than that of the saline group on day 7, and day 28(P<0.01, P<0.001). Microvessel density in the wound skin of Bevacizumab group appeared to be significantly lower than that of the saline group (P<0.01). Conclusion The injection of Bevacizumab may delay the wound healing by inhibiting the angiogenesis in the new skin tissue of the cynomolgus monkey. In clinical practice, the timing of giving a tumor patient a bevacizumab injection after surgery should be based on the pros and cons, and the duration, dosage, and frequency of the intervention should be chosen in a rational way. Table and Figures | Reference | Related Articles | Metrics

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Establishment of a Vaginal Atrophy Rat Model and its Application in Pharmacodynamic Evaluation Liya YANG, Tao SONG, Jialin HE, Yiming GUO, Mingkang QI, Hanbi WANG, Huiping WANG Laboratory Animal and Comparative Medicine    2022, 42 (6): 531-540.   DOI: 10.12300/j.issn.1674-5817.2022.014 Abstract （714）   HTML （31）    PDF （1810KB）（1478）       Knowledge map    Save Objective To establish an animal model suitable for screening vaginal preparations, administering the corresponding drugs, and evaluating biological indicators for monitoring drug treatment effects. Methods Bilateral ovariectomy (OVX) was used to establish the disease model of rat. The estrous cycle, uterine wet weight, and vaginal tissue morphology were observed from day 15 to day 21 after OVX to determine the optimal time for successful vaginal atrophy model after the OVX operation. Sprague-Dawley female rats were randomly divided into the following groups: normal group, sham group, model group, drug group 1, drug group 2, and solvent control group (n=10). Drug group 1, drug group 2, and solvent control group were treated with promestriene, Colpotrofin?, and solvent control for 14 days, respectively. Three days after the last administration, the body weight and uterus wet weight of the rats were measured, the histological morphology of the vagina was analyzed by HE staining, and estrogen receptors-α (ERα) expression was detected by immunohistochemistry. Results Twenty-one days after OVX, the vaginal atrophy model was established, which was suitable for the follow-up experiments. The change of estrous-cycle wasn't observed from day 17 to 21 after OVX. On 21 days after OVX, the vaginal epithelium thickness reduced (P<0.05), vaginal folds reduced, no squamous epithelium was observed, body weight increased (P<0.05), and uterine wet weight decreased (P<0.05). In drug group 1 and drug group 2, the symptoms of vaginal atrophy improved. Compared with the model group, the body weight of rats in drug group 1 and 2 decreased (P<0.05), the vaginal histomorphology improved, the expression of ERα protein in vaginal tissue up-regulated (P<0.05), and the ratio of uterine wet weight to body weight increased (P<0.01), but the endometrial thickness was not significantly thickened (P>0.05). Conclusion The rat OVX model is suitable for screening vaginal preparations. Vaginal histomorphology, endometrial thickness, and uterine/body weight ratio can be used as indicators to monitor drug efficacy. Table and Figures | Reference | Related Articles | Metrics

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Construction of Lipopolysaccaride Binding Protein Knockout Mice Using CRISPR/Cas9 Technology Sidi LI, Bin FU, Zhongkun GUO, Yingjie LIN, Zhenyu ZHANG, Chuanliang MI, Kezhou WANG Laboratory Animal and Comparative Medicine    2022, 42 (4): 294-300.   DOI: 10.12300/j.issn.1674-5817.2022.002 Abstract （712）   HTML （404）    PDF （1137KB）（983）       Knowledge map    Save Objective To construct a stable hereditary lipopolysaccaride binding protein (Lbp) gene knockout mice by using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) gene editing technology. Methods According to the sequence characteristics of Lbp gene in C57BL/6J mice, the target of sgRNA was designed, the 5'-end protein coding conserved sequence of Lbp gene was deleted and the shift mutation was introduced to inactivate LBP. The genome of F0, F1, F2, F3 generation mice was extracted; PCR was used to identify and sequence Lbp knockout; RT-PCR was used to verify Lbp gene transcription, and Western blotting was used to verify LBP protein expression in F2 generation. Results Five Lbp+/- mice from F0 generation, three Lbp+/- mice from F1 generation, four Lbp-/- mice from F2 generation and thirty Lbp-/- mice from F3 generation were obtained. RT-PCR showed that Lbp-/- mice mRNA was 244 bp and the translation was stopped early by code-shifting mutation. Western blotting showed that LBP protein was not expressed in the liver of Lbp-/- mice. Conclusion The Lbp gene knockout mice were successfully constructed by CRISPR/Cas9 technique, which will provide a basis for further study of the immune and physiological effects of LBP. Table and Figures | Reference | Related Articles | Metrics

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Establishment and Evaluation of a Rat Model of Non-Puerperal Mastitis YIN Yulian, MA Lina, TU Siyuan, CHEN Ling, YE Meina, CHEN Hongfeng Laboratory Animal and Comparative Medicine    2024, 44 (6): 587-596.   DOI: 10.12300/j.issn.1674-5817.2024.065 Abstract （707）   HTML （248）    PDF （1898KB）（732）       Knowledge map    Save Objective This study aims to establish a non-puerperal mastitis (NPM) rat model by simulating hyperprolactinemia and immune-inflammatory states, and to evaluate its local inflammatory characteristics in the mammary gland, thereby laying the foundation for research on the diagnosis and treatment of this clinically challenging disease. Methods Twelve SPF-grade Wistar female rats were evenly divided into a control group and a model group. During the experiment, the control group received no experimental treatment or medication. The model group received daily subcutaneous injections of 100 mg/kg metoclopramide hydrochloride for 7 consecutive days. Serum prolactin (PRL) levels were measured using ELISA on the 10th, 20th, and 30th days after the first injection. After 7 days of injections, 200 μL of lactating SD rat milk was mixed with 200 μL of complete Freund's adjuvant to prepare an oil-in-water emulsion, which was administered by multiple subcutaneous injections into the back of the Wistar rats for the initial immunization. Seven days after the initial immunization, the emulsion was injected subcutaneously into the third, fourth, and fifth mammary glands for the final immunization. After the final immunization, the rats were observed for 28 days for changes in mammary gland appearance, and the size of mammary nodules was calculated. On the 3rd, 7th, 14th, and 28th days, hematoxylin-eosin (HE) staining was used to analyze mammary tissue morphology. Immunohistochemistry was employed to detect CD138 expression levels. ELISA was used to measure the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) in mammary tissue to comprehensively assess the model. Results Rats in the model group exhibited mammary skin ulceration and foul odor at the ulcer sites. Palpation and ultrasound revealed the formation of mammary nodules. HE staining showed that on the 3rd day after the final immunization, normal ductal and lobular structures in the mammary glands disappeared, with significant infiltration of plasma cells. On the 7th day, ductal dilation, epithelial necrosis and detachment, and pronounced periductal plasma cell and lymphocyte (predominantly T-lymphocytes) infiltration were observed. On the 14th day, there was a proliferation of fibrofatty tissue, small blood vessels, and granulation tissue, with scattered plasma cells in the interstitium. By the 28th day, inflammatory cell infiltration and fibrous tissue proliferation were reduced, with granuloma formation. Serum PRL levels in the model group were significantly increased on the 10th day (P<0.05) and the 20th day (P<0.001). IL-6 and TNF-α levels in mammary tissue were higher in the model group compared to the control group on the 3rd, 7th, 14th, and 28th days (P<0.05). IL-1β levels were higher on the 3rd, 7th, and 14th days compared with the control group (P<0.01) but lower than the control group on the 28th day (P>0.05). iNOS levels were significantly higher on the 7th day after the final immunization (P<0.001). Conclusion A successful NPM model was established in rats, which exhibited typical pathological features such as local mammary masses, abscesses, ulcers, ductal dilation and plasma cell infiltration. This model can serve as a foundation for further research into the diagnosis and treatment of this clinically challenging disease. Table and Figures | Reference | Related Articles | Metrics

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Establishment of a Rabbit Heart-failure Model Using Transverse Aortic Constriction Qingyi LUO, Tiling ZHANG, Yunchuan DING, Jian CHEN, Li ZHAO, Qinghui WANG Laboratory Animal and Comparative Medicine    2022, 42 (5): 401-408.   DOI: 10.12300/j.issn.1674-5817.2022.020 Abstract （706）   HTML （27）    PDF （1859KB）（941）       Knowledge map    Save Objective To investigate the method and feasibility of establishing a rabbit heart-failure model using transverse aortic constriction (TAC). Methods Twenty-five healthy male Japanese white rabbits were randomly divided into an operation group (n=15) and a sham-operation group (n=10). The animals in the operation group underwent TAC to establish the rabbit model of heart failure. The sham-operation group underwent thoracotomy but no narrowing operation. Cardiac function was evaluated using ultrasound at 4 and 8 weeks after operation. Eight weeks after operation, the descending aortic flow velocity was detected using cardiac ultrasound, combined with molecular biological indexes and pathological observations to verify the feasibility and stability of TAC in establishing the rabbit heart-failure model. Results Eight weeks after operation, 13 rabbits in the operation group and 10 in the sham-operation group survived. The blood flow velocities at the constriction in the operation group were >2.20 m/s. Compared with the sham-operation group, the following outcomes in the operation group increased significantly (P<0.05): heart rate, ascending aortic diameter, left atrial end-diastolic diameter, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter. Left ventricular ejection fraction decreased significantly (P<0.05). Compared with the sham-operation group, the contents of left ventricular N-terminal pro B type natriuretic peptide (NT-proBNP) and β-myosin heavy chain (β-MHC) significantly increased in the operation group (P<0.05). Pathological sections showed that 8 weeks after TAC, cardiomyocytes in the operation group were hypertrophic and disordered, and myocardial fiber bundles widened. Interventricular septal end-diastolic thickness and left ventricular posterior wall end-diastolic thickness significantly increased in the operation group (P<0.05), compared to those in the sham-operation group at 4 weeks. Conclusion It is effective and feasible to establish an experimental rabbit heart-failure model using TAC. Cardiac ultrasound is an effective method to evaluate and determine the degree of aortic arch constriction and the success of heart-failure modeling. Rabbits in the operation group showed myocardial decompensation at 8 weeks after TAC, resulting in irreversible heart failure. Table and Figures | Reference | Related Articles | Metrics

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Research Progress on Animal Models of Intrauterine Growth Restriction Qiwen HU, Zheng BI, Haiping LIU, Zhihua DONG, ZHUYanlin, Jinhua WANG Laboratory Animal and Comparative Medicine    2022, 42 (5): 423-431.   DOI: 10.12300/j.issn.1674-5817.2022.063 Abstract （705）   HTML （43）    PDF （883KB）（5353）       Knowledge map    Save The occurrence of intrauterine growth restriction (IUGR) may be related to maternal malnutrition, abnormal placental function, immune abnormalities, genetically related problems as well as other diseases, but the mechanism is still unclear. Therefore, the study of IUGR and the development of its animal model are critical issues in obstetrics. IUGR models are mainly based on laboratory rodents, such as mice and rats, and other mammals such as pigs, rabbits and sheep. This article introduced several common IUGR animal models, including nutrition restriction model, high-altitude pregnancy model, natural selection model, and nicotine exposure model, and also described the construction methods of IUGR models and the comparison of their advantages and disadvantages. Table and Figures | Reference | Related Articles | Metrics

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Physiological Indexes and Histopathology Analysis of Sodium Iodate-Induced Retinitis Pigmentosa in Rats Ying TAN, Wenping LIAO, Qilong GAO, Yong LI, Xinhui SHI, Jingkun WANG Laboratory Animal and Comparative Medicine    2023, 43 (2): 124-135.   DOI: 10.12300/j.issn.1674-5817.2022.149 Abstract （699）   HTML （45）    PDF （3691KB）（2147）       Knowledge map    Save Objective To evaluate the effects of intraperitoneal injection of sodium iodate on the physiological indexes and retinal histopathological characteristics of SD rats comprehensively. Methods A total of 64 rats were randomly divided into negative control group and model group, half male and half female. The model group was intraperitoneally injected with 6 mg/mL sodium iodate once at the dose of 10 mL/kg and the negative control group was injected with 10 mL/kg 0.9% NaCl once. The body weight of all surviving rats was detected on the day of injection (0 day) and the 2nd, 6th, 9th, 13th, 16th, 20th, 23rd, 27th, 29th, 36th, 43rd, 50th and 57th days after injection. On the 3rd, 7th, 21st, 28th, 41st and 62nd days after injection, the rats were randomly selected (12 rats in each group on the 28th day, and 4 rats in each group at other time points, those in each group were half male and half female) for serum biochemical indexes detection. The organs were dissected and weighed, and then the main organs and tissues were stained with HE, and the eyes were stained with HE and TUNEL. Blood routine indexes were detected on the 28th and 62nd day after injection. Results After injection of sodium iodate, 88% of the rats in the model group had transient loose stools. During the observation period, the body weight of the rats increased slightly and was more obvious in male rats. On the 28th day after injection, compared with the negative control group, the red blood cell volume (RDW) of female rats and blood urea nitrogen (BUN), reticulocyte count (Retic#) and reticulocyte percentage (Retic%) of male rats in the model group increased significantly (all P＜0.05). The white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and hematocrit (HCT) of male and female rats showed decreasing trends, but there were no significant differences between the two groups (all P >0.05). The thymus weight and coefficient of male rats in the model group were smaller than those in the negative control group except for the 7th day after injection, but there were no significant differences between the two groups (all P ＞0.05). Histopathological examination showed that the retina of the model group gradually developed from wavy changes to abnormal electrocardiogram (ECG)-like changes, with disordered arrangement of each layer, focal thinning of the outer nuclear layer, and apoptosis of the outer nuclear layer of the retina. The incidence of lesions, lesion score and the number of apoptotic cells in the model group were significantly higher than or more than those in the negative control group at the same time, and the difference between the groups on the 28th day was statistically significant (all P＜0.01). Conclusion In addition to retinal degeneration in rats, intraperitoneal injection of sodium iodate also had a certain degree of influence on serum biochemical and blood routine indexes, and also showed a slight slow growth of body weight and transient changes in fecal traits. Therefore, when using this model to evaluate drug safety, the effects of modeling reagents on animals should be paid to attention. Table and Figures | Reference | Related Articles | Metrics

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Inhibition of Phospholipase D1 Activity Improves the Recovery of Neurological Function in Mice with Ischemic Stroke Yanbing ZHU, Fan BAI, Shaoxin TAO, Yuhualei PAN, Huan WANG, Yushang ZHAO, Song WANG, Yan YU Laboratory Animal and Comparative Medicine    2022, 42 (4): 322-332.   DOI: 10.12300/j.issn.1674-5817.2022.041 Abstract （697）   HTML （362）    PDF （1895KB）（769）       Knowledge map    Save Objective To investigate the dynamic changes of autophagy in infarcted cortex at different stages after ischemic stroke, and the relationship between phospholipase D1 (PLD1) activity, autophagy, and the neurological function in mice. Methods Firstly, twenty-one male C57BL/6 mice at age of 8 weeks were used to establish ischemic stroke models, and they were randomly divided into sham surgery and ischemic stroke groups. The groups were furtherly divided into 4-, 6-, 8-, 12-, 24-, and 72-hour groups according to the onset of ischemic strok with three mice in each group. Dynamic expression and change of autophagy-related protein LC3 in the infarcted cortex were observed using Western blotting method and immunofluorescence staining. Secondly, thirty-six male C57BL/6 mice at age of 8 weeks were randomly divided into the sham surgery group, the PBS treatment group, and different concentrations of phospholipase D activity inhibitor 5-fluoro-2-indolyl des-chlorohalopemide (FIPI) treatment groups containing 0.3, 0.9, 1.8, and 3.6 mg/kg, respectively. Each group comprised six mice. The optimal FIPI concentration and its effects on neurological function and infarcted volume were assessed by adhesive removal and whisker tests and TTC staining. Furthermore, nine male C57BL/6 mice at age of 8 weeks were divided into sham surgery group, intraperitoneal administration of PBS group, and 0.9 mg/kg FIPI group. Each group comprised three mice. The effects of FIPI on changes in autophagy-related protein LC3 were examined by Western blotting. Finally, thirty-six adult male C57BL/6 mice at age of 8 weeks were divided into sham surgery group, intraperitoneal administration of PBS group, and 0.9 mg/kg FIPI treatment groups at four time points (0, 4, 8, and 12 hours) after ischemic stroke. Furthermore, the neurological functions and infarcted volume were assessed by the adhesive removal and whisker tests as well as TTC staining with six mice in each group. Results The ratio of LC3-Ⅱ/β-actin in the infarcted cortex increased, peaked at 24 hours (P＜0.05), and then gradually declined after ischemic stroke. Compared with the PBS group, the administration of 0.9 mg/kg FIPI significantly decreased the ratio of LC3-Ⅱ/β-actin (P＜0.05), reduced the infarcted area (P＜0.05), and ameliorated neurological functions (P＜0.05) more than those observed in the other concentration groups. Compared with the PBS group, in addition to 0.9 mg/kg FIPI without delay, the administration of 0.9 mg/kg FIPI at 4-, 8-, and 12-hour after ischemic stroke could also decrease the infracted volume (P＜0.05) and improve the neurological function (P＜0.05). Conclusion The change of autophagy was the most obvious at 24-hour after ischemic stroke and inhibition of PLD1 could improve the recovery of neurological function after ischemic stroke. Meanwhile, in addition to administration of 0.9 mg/kg FIPI without delay, 4-, 8-, and 12-hour after ischemic stroke could also shrink the infracted volume and improve the neurological function. The inhibition of the PLD1 could extend the therapeutic window and provide a novel therapeutic strategy for the clinical treatment of cerebral stroke. Table and Figures | Reference | Related Articles | Metrics