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    A Comparative Analysis of CNAS Laboratory Animal Institutions Accreditation and AAALAC Certification
    Xiaohuai WU, Qiaozhe XIAO, Wanyong PANG, Yu BAI, Yao LI, Xuancheng LU, Tao FENG
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 237-243.   DOI: 10.12300/j.issn.1674-5817.2022.033
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    China National Accreditation Service for Conformity Assessment (CNAS) laboratory animal institutions accreditation is an important system for the management of laboratory animals in China. It is a third-party evaluation on Chinese characteristics dedicated to ensuring the quality and welfare of laboratory animals in China. The American Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) certification provides global services about animal welfare evaluation and ethical certification, which are important for management and use of laboratory animals. This study compared and analyzed the nature of CNAS and AAALAC, the nature of CNAS accreditation and AAALAC certification, the evaluation principles, required documents, the evaluation process, the management of reviewers, and the acceptance of results, and discussed the differences and characteristics of the two evaluation systems for laboratory animal institutions.

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    Research Progress in Animal Models of Ulcerative Colitis
    Yu HU, Yunxi LAN, Xiaoxiao CHEN, Wei XIONG, Songqi TANG, Bo JIA, Wei HUANG
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 220-228.   DOI: 10.12300/j.issn.1674-5817.2021.155
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    Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease. Its pathogenesis has not been fully revealed. Moreover, the lack of effective and safe treatment strategies is an obstacle for UC treatment currently. Animal models are essential tools in disease research. Therefore, the establishment of animal models with pathological manifestations similar to human UC is conducive to the full study of this disease. In this review, we reviewed the research progress of animal models of UC, and found that chemical induction is the most commonly used method for modeling UC. Based on the development of genomics technology, gene editing or knockout-induced spontaneous colitis is a vital direction for animal models research in the future. In addition, the indexes for evaluating the modeling results of UC animal models need to be further explored.

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    A Comparative Study of Chronic Obstructive Pulmonary Disease Rat Models Established by Different Methods
    Xinpeng LU, Rong LIU, Wenbo Huang, Jin ZHAO, Hongtao LI
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 201-206.   DOI: 10.12300/j.issn.1674-5817.2021.118
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    Objective To compare the effects and characteristics of cigarette smoke exposure (CSE) alone and CSE combined with airway instillation of bacterial lipopolysaccharide (LPS) in chronic obstructive pulmonary disease (COPD).Methods Male SD rats were randomly divided into control, CSE, and CSE+LPS groups, with 10 rats in each group. After 24 weeks, the models were established and the lung function of the rats was measured. Hematoxylin-eosin (HE) staining was performed to observe the pathological changes in the airway and lung tissue. The ELISA method was used to detect the level of serum interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) in peripheral blood.Results Airway resistance (RI), functional residual capacity (FRC), and chord compliance (Cchord) of the CSE and LPS+CSE groups were higher than those of the control group (all P < 0.05), while the tidal volume (TV), minute volume (MV), and forced expiratory volume in 50 ms (FEV50) / forced vital capacity (FVC) of the CSE and LPS+CSE groups were lower than those of the control group (all P < 0.05). HE staining of lung tissue showed that the average alveolar intercept and thickness of the small airway walls were higher in the CSE and LPS+CSE groups than those in the control group. Compensatory enlargement was evident in the alveolar cavity of the CSE and CSE+LPS groups, and the alveolar septum widened, with a fusion of pulmonary alveoli in the CSE+LPS group. The levels of IL-8 and TNF-α in serum of the CSE and CSE+LPS groups were higher than those of the control group (all P < 0.05). The level of TNF-α in serum of the CSE+LPS group was higher than that of the CSE group (P < 0.05).Conclusion The CSE combined with LPS method is superior to CSE alone for establishing the COPD rat model, and the combined model is closer to clinical manifestations.

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    Efficacy of DZ1462, a Novel Sodium-phosphate Transporter Inhibitor, on 5/6 Nephrectomy-induced Hyperphosphatemia Model Rats
    Xiao LU, Lin ZHANG, Hui JI, Shanxiang JIANG
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 187-193.   DOI: 10.12300/j.issn.1674-5817.2021.138
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    Objective To study the efficacy of DZ1462, a novel sodium-phosphate transporter inhibitor, on rat hyperphosphatemia models established by 5/6 nephrectomy.Methods Totally 156 rats were randomly selected into four groups. Rats fed a normal diet were control group, named as group Ⅰ (n=6); rats fed a normal diet after 5/6 nephrectomy were named as group Ⅱ (n=60); rats fed a high phosphate diet after 5/6 nephrectomy were named as group Ⅲ (n=60); rats fed a high phosphate diet after sham surgery were named as group Ⅳ (n=30). The molding cycle was 10 weeks. Serum Pi was detected and the number of animal deaths was recorded every two weeks. Hematoxylin-eosin (HE) staining was performed to observe the change in kidney pathology, and to screen animal models with high phosphorus blood syndrome. Totally 18 model rats that met the inclusion criteria (all of group Ⅲ) were selected and randomly assigned to three groups: the model control group recorded as the G2 group; the DZ1462 administration group (30 mg/kg, tid, 21 d) recorded as the G3 group; the Sevelamer administration group (250 mg/kg, tid, 21 d) recorded as the G4 group. In addition, the normal control group was set as the G1 group. Serum phosphate levels were measured using a kit.Results In the 8th and 10th weeks, compared to group Ⅰ, serum phosphorus in group Ⅲ showed a significant difference (P < 0.01). The kidneys in group Ⅲ had obvious glomerular sclerosis, renal tubular atrophy, degeneration, interstitial inflammation, fibrosis, and calcification. Similarly to chronic kidney disease accompanied by hyperphosphatemia, the animal model was established successfully. At each time point, the serum phosphorus inhibition rate of the G3 group was significantly higher than that of the G4 group (P < 0.05).Conclusion DZ1462, as a novel small-molecule inhibitor of intestinal sodium and phosphorus transporter, can effectively inhibit intestinal phosphorus ion absorption in rat hyperphosphatemia model, and is expected to become a potential drug for the clinical treatment of hyperphosphatemia.

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    Construction Methods and Influencing Factors on Animal Model of Sepsis
    Xiao LI, Haipeng YAN, Zhenghui XIAO
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 207-212.   DOI: 10.12300/j.issn.1674-5817.2021.121
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    Sepsis is a common acute and critical illness, and its pathogenic mechanism is complex, often involving multiple organs and systems in the body. Various factors such as inflammatory response, immune dysfunction, and coagulation dysfunction are connected into an interconnected and mutually influencing network system, aggravating the severity of the disease. At present, the case fatality rate of sepsis is about 25%, which is a serious threat to human health. Establishing a stable and reliable experimental animal model of sepsis is an important means to understand the mechanism of host defense regulation in the early stage of infection, the mechanism of host response disorder in the stage of disease progression and to study the therapeutic effect of new therapeutic drugs. At present, there are many methods to establish animal models of sepsis, and there are many influencing factors. Therefore, this paper reviewed the preparation methods and influencing factors of animal models of sepsis, in order to provide some references for researchers to select suitable animal models.

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    Anatomical Characteristics and Background Lesions in Laboratory British-shorthair Cats
    Yu WANG, Dan GAO, Nana PENG, Ai HANG, Bin SHEN, Jian HUANG, Liming TANG
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 229-236.   DOI: 10.12300/j.issn.1674-5817.2021.151
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    Objective To investigate anatomical characteristics and background lesions in laboratory British-shorthair cats (BSCs) through gross and histopathological examination, and provide effective basis for the research and application, standard establishment and market promotion of this experimental animal. Methods Gross system dissection and histopathological examination were performed on 14 adult BSCs (half male and half female), and the histological characteristics and background pathological data were collected and analyzed. Results The body weight and organ index of spleen of BSCs was higher in males than females (P < 0.05, P < 0.01), the organ coefficients of brain and thymus in BSCs were lower in males than females (P < 0.05). The anatomical structure of testicles, heart, thyroid gland and tentorium of BSCs is different from that of rodents and canine. Furthermore, histopathological examinations revealed that the structures of heart, pancreas, spleen in BSCs differed from two experimental animals mentioned above. In addition, there were multiple hepatic cell vacuolar degeneration in BSCs (9/14), and occasional renal, brain and lymphoid tissues were also found in some animals. Conclusion There were six differences in body weight, and organ-coefficient of spleen, thymus, and brain in BSCs, while the hepatocyte phospholipidosis of liver and background lesion in BSCs were found.

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    Characteristics and Application of Transgenic Mouse Models in Alzheimer's Disease
    Feng WEI, Weiwei CHENG, Yafu YIN
    Laboratory Animal and Comparative Medicine    2022, 42 (5): 432-439.   DOI: 10.12300/j.issn.1674-5817.2021.182
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    Alzheimer's disease is a common neurodegenerative disease characterized by progressive memory loss and overall cognitive decline. Two typical pathological features are senile plaques and neurofibrillary tangles detected in the brain, which consist of large amounts of precipitated amyloid peptide and hyperphosphorylated Tau protein, respectively. In addition, there are other pathological features such as neuroinflammatory response and extensive loss of neurons. In the past decades, a lot of research has been done on Alzheimer's disease, but its etiology and pathogenesis are still unclear, and there is no ideal treatment or radical cure. This review introduced the characteristics of various transgenic animal models and their current application in preclinical studies, in order to provide theoretical basis for future experimental studies.

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    Comparison of the Anesthetic Effects of Different Doses of Ketamine Hydrochloride Combined Xylazine on Short-term Anesthesia in Bama Miniature Pigs
    Chen SHEN, Baojie ZHANG, Xuemin WANG, jinyan ZHU, Min ZHANG, Bin LI
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 262-265.   DOI: 10.12300/j.issn.1674-5817.2021.127
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    Objectives To perform the combined anesthesia of ketamine hydrochloride and xylazine in miniature pigs, and to analyze the effect of drug dose on anesthesia.Methods Thirty-six Bama miniature pigs were randomly divided into three groups. Group A was administered with ketamine hydrochloride (10 mg/kg) + xylazine (2 mg/kg). Group B was administered with ketamine hydrochloride (10 mg/kg) + xylazine (1.5 mg/kg). Group C was administered with ketamine hydrochloride (5 mg/kg) + xylazine (2 mg/kg), and anesthesia monitoring indexes were recorded.Results There were no significant differences in anesthesia onset time and awake time between groups A and B (P > 0.05), and the awake time of anesthesia in groups A and B was significantly longer than that in group C (P < 0.05).Conclusion Ketamine hydrochloride (10 mg/kg) combined with xylazine (1.5?2 mg/kg) anesthesia has a rapid effect, stable anesthesia depth, no obvious movement, and satisfactory safety. It can be used in short procedures, diagnoses, and treatments.

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    Research Progress on Alternative Methods of Skin Sensitization Test
    Jingyi HUANG, Peining LI, Xiangmei LIU, Zhonghua LIU, Yufeng HUANG
    Laboratory Animal and Comparative Medicine    2022, 42 (4): 313-321.   DOI: 10.12300/j.issn.1674-5817.2021.173
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    Allergic contact dermatitis is a type Ⅳ hypersensitivity reaction caused by repeated skin exposure to a substance and is a common public health problem. Traditional skin sensitization tests are based on animal experiments such as guinea pig maximum test and closed patch. In recent years, with the increasing attention of animal ethics and the development of science and technology, alternative methods of skin sensitization test have emerged. According to different principles, these alternative methods are divided into in vivo alternative methods, several in vitro alternative methods based on harmful outcome pathways, and genomic allergen rapid test, etc. In this paper, we reviewed the progress of these alternative methods of skin sensitization test, and several integrated testing and evaluation methods based on adverse outcome pathways.

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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
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    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.

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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
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    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.

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    Discussion on the Problems and Methods of Animal Laboratory Documents Management from the Perspective of Audit
    Haiyu LI, Hufeng XU
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 244-247.   DOI: 10.12300/j.issn.1674-5817.2021.114
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    Hospital established a good animal experiment platform and a complete set of animal experiment management systems. In good operation, document management is a key element. This paper aimed to improve the management of animal laboratory documents from the perspective of the laboratory accreditation and testing institution accreditation auditor of the China National Accreditation Service for Conformity Assessment (CNAS), and provides a reference for the improvement of the management level of relevant practitioners.

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    The Latest Research Progress of the Function of Spinal CD11c + Microglia in Neuropathic Pain
    Changgeng PENG, Yan FU, Fengting ZHU, Ruilong XIA, Wei XIA
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 171-176.   DOI: 10.12300/j.issn.1674-5817.2022.073
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    Neuropathic pain (NP) affects approximately 10% of the population, and treatments and drugs for NP have limited efficacy. Microglia in the spinal cord play important and paradoxical roles in peripheral nerve injury-induced NP, both promoting the development of NP and relieving NP. In April 2022, Keita Kohno et al. reported that after peripheral nerve injury, CD11c+ microglia appearing in the spinal cord of mice were a type of microglia that relieve NP and inhibited pain recurrence. In this commentary, we review the important findings of this type of analgesic microglia subset, and provide a perspective for future work related to this new finding.

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    Recent Advances of Animal Models of Renal Interstitial Fibrosis
    Can LAI, Lele LI, Tala HU, Yan MENG
    Laboratory Animal and Comparative Medicine    2023, 43 (2): 163-172.   DOI: 10.12300/j.issn.1674-5817.2022.171
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    Renal interstitial fibrosis is a common pathway in the progression of many renal diseases. Whether it is chronic kidney disease or acute kidney injury that cannot be fully recovered, the progression process mostly enters end-stage renal failure after renal interstitial fibrosis. The animal model of renal interstitial fibrosis is an important research tool for exploring the pathogenesis of renal interstitial fibrosis and new diagnostic and treatment methods. Different animal models have their own characteristics. Researchers can establish different models based on their own experience and experimental purposes, and carry out scientific research on this basis to provide more new methods for the prevention and treatment of kidney diseases. The authors focused on several common animal models of renal interstitial fibrosis to provide the reference for related researchers, including surgical models induced by unilateral ureteral obstruction, ischemia-reperfusion injury, 5/6 nephrectomy, and microembolization; chemical models induced by cyclosporine A, adriamycin, aristolochic acid, mercuric chloride(HgCl2), gentamicin, cisplatin, and adenine; transgenic hybridization and kidney injury molecule 1 (KIM-1) induced transgenic modification model; composite model induced by bilateral ischemia-reperfusion injury (BIRI) combined with gentamicin, unilateral nephrectomy combined with angiotensin II (Ang II), and unilateral ischemia-reperfusion injury (UIRI) combined with pLVX-shTNC plasmid.

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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
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    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.

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    Injurious Effect of Cisplatin on the Function of Hypothalamus-pituitary-adrenal/gonadal Axis in Mice and the Intervention Effect of Dehydroepiandrosterone
    Zhiqiang PAN, Zixin NONG, Haina XIE, Peike PENG
    Laboratory Animal and Comparative Medicine    2023, 43 (3): 229-242.   DOI: 10.12300/j.issn.1674-5817.2022.182
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    Objective To study the pathway of cis-dichlorodiamineplatinum (DDP) inhibiting the synthesis of steroid hormones in mice, and to observe the intervention effect of dehydroepiandrosterone (DHEA). Methods Sixty adult ICR mice were randomly divided into three groups: control group, DDP modeling group, and DHEA group, with 10 male and 10 female mice in each group. The DDP modeling group mice were intraperitoneally injected with DDP solution at a dose of 2.5 mg·kg-1·d-1, once every 3 days, a total of 7 times. On the same day of modeling, the control group mice were injected with an equal amount of physiological saline intraperitoneally. The DEHA treatment group mice were treated with DDP and given a dose of 8.3 mg·kg-1·d -1 of DHEA by gavage for 21 consecutive days. The changes of fatigue indexes of mice were observed by open field, grip and rod rotation tests. The morphology changes of adrenal gland, testicular and ovarian tissue were observed by pathological section and HE staining. The levels of serum steroid hormones were detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The mRNA and protein expression levels of the related genes of the hypothalamus, hypophysis, adrenal, testis and ovary were tested by real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting. Results Compared with control group, both male and female mice in DDP modeling group were significantly losing weight (P<0.05), their abilities in horizontal movement and vertical movement decreased (all P<0.05), and the stay time and grip also significantly decreased (all P<0.05) in female mice. Indexes of fatigue were improved after DHEA supplement (all P<0.05). In the DDP modeling group, the arrangement of spermatogenic cells at all levels in the testicular tissue was disordered and the testicular interstitial edema was observed, and a large number of primordial follicles in the ovarian tissue were activated, the number of atresia follicles increased, and the number of granulosa cells in the follicles decreased; while in the DHEA group, the damaged phenotype of testicles and ovaries was significantly improved. Compared with control group, the levels of serum testosterone and dihydrotestosterone in both male and female DDP modeling mice significantly decreased (P<0.01), the pregnenolone was down-regulated but corticosterone was up-regulated significantly (P<0.05) in male mice, the corticosterone was down-regulated significantly (P<0.05) in female mice. Compared with the DDP group, after DHEA supplement, the pregnenolone in male mice and the progesterone in female mice increased significantly (P<0.05), but the pregnenolone in female mice and the progesterone in male mice decreased significantly (P<0.05). Compared with control group, the expression levels of Cyp21a1 and Cyp11a1 genes in the adrenal gland and Gnrh gene in the hypothalamus of male and female mice in the DDP modeling group significantly decreased (all P<0.05); the expression levels of Hsd3b2 gene in the adrenal gland, Star, Cyp11a1, and Lhr genes in the ovaries, Crh, Pomc, and Lhb genes in the hypothalamus, pituitary, and pituitary of female mice significantly decreased (all P<0.05); the expression levels of Star gene and StAR protein in the testicles of male mice, as well as Fshb and Lhb genes in the pituitary gland, were significantly down-regulated (all P<0.05). After DHEA supplement, compared with the DDP modeling group, the mRNA expression levels of Cyp17a1 in the adrenal gland of male mice and Cyp17a1, Lhr and Fshr genes in testis were down-regulated significantly (P<0.05); the expression level of Cyp11a1 gene in the adrenal gland of female mice was also decreased (P<0.05); while the expression levels of Hsd3b2 gene in the adrenal gland, Star, Cyp11a1, Hsd3b2 and Lhr gene in the ovary, and Lhb gene in the pituitary gland were all up-regulated ( P<0.05). Conclusion The function of hypothalamus-pituitary-adrenal/gonadal axis was inhibited by DDP intermittent injection, especially in female. Supplementation of DHEA can help regulate the homeostasis of steroid hormone levels.

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    Analysis on the Development Status of Laboratory Animals in Japan
    Huan GOU, Xinying AN, Yujia TONG, Yan WANG, Shuang YANG
    Laboratory Animal and Comparative Medicine    2023, 43 (2): 194-204.   DOI: 10.12300/j.issn.1674-5817.2022.141
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    Experimental animals have made important contributions to human medical research and life and health. It is known that the development of laboratory animal science in Japan has been relatively rapid in the past few decades, providing important support for the development of the world's experimental animal field. Therefore, it is of great significance to understand the management mode and resource storage situation of Japanese experimental animals, analyze the advantages of Japanese experimental animal development, and propose suggestions to strengthen the high-quality development of experimental animals in China. Through literature research, the authors first analyzed the management system of experimental animals in Japan, including regulations and policies, research funding management, experimental animal management, talent cultivation, and standard and normative systems. Then, the current status of experimental animal research in Japan was summarized, including experimental animal resources, major research institutions, and production enterprises. On this basis, it was found that the field of experimental animal research in Japan currently exhibits characteristics such as a complete policy system, flexible management methods, rich resource reserves, and large-scale industrial development. Finally, by comparing the existing problems in China, suggestions for the development of experimental animal technology in China are proposed: (1) drawing on the legal management method of experimental animals in Japan, strengthening and improving the legislation and management model of experimental animals in China; (2) increaseing investment in scientific research funds, playing the role of research institutions, societies and industries, and promoting the incremental construction and industrial development of experimental animal resources.

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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
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    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.

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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
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    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.

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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
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    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.

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    Application of Gastric Cancer Organoids in Precision Medicine Research
    Miaomiao GONG, Ligui ZHOU, Jumei ZHAO, Changhong SHI
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 248-254.   DOI: 10.12300/j.issn.1674-5817.2021.159
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    Organoid is an in vitro three-dimensional culture system of stem cells or tissues derived from patients. Both normal gastric organoids and gastric cancer organoids can be established through this culture technique. Organoid possesses high fidelity, it grows with the similar molecular structures, functional characteristics, and genetic information as its tissue-of-origin. According to above, organoid can perform therapeutic targets screen, facilitate drug responses prediction and verification. Meanwhile, it also provides a new idea for precision medicine research of gastric cancer and replacement research of laboratory animals. This paper reviewed the establishment of organoid model of gastric cancer and the development of application of organoid in precision medicine, to provide ideal in vitro models reference for precision medicine research of gastric cancer.

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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
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    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.

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    Pathological and Synaptic Morphological Changes of the Olfactory Bulb in APP/PS1 Model Mice at Different Ages and the Intervention Effect of Memantine
    Jiani LIU, Jiangang LIU, Yun WEI, Hao LI, Zenggang LUO, Yi WANG, Kun LI
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 177-186.   DOI: 10.12300/j.issn.1674-5817.2022.001
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    Objective To compare and explore the histopathological and ultrastructural characteristics of the olfactory bulb in 6- and 12-month-old APP/PS1 double-transgenic mice and their spatial learning and memory ability, as well as the effects of memantine intervention.Methods Three-month-old SPF male APP/PS1 mice were randomly divided into 6- and 12-month-old model groups (named 6-APP/PS1 group and 12-APP/PS1 group, respectively) and memantine (MEM) groups (named 6-MEM group and 12-MEM group, respectively, the dose of MEM was 2.60 mg/kg/d), with 10 mice in each group. Age-matched C57BL/6 mice were used as the blank controls. The mice in the MEM groups were continuously administered MEM (from 3 months and 9 months, respectively) by gavage for 3 months, and the mice in the non-MEM group received equal volume of pure water for 3 months. The Morris water maze test was used to assess spatial learning and memory ability of those mice at 6 months and 12 months of age. After hematoxylin-eosin staining, the pathological morphology of the olfactory bulb was observed under an optical microscope, and the ultrastructure of the olfactory bulb was observed under a transmission electron microscope.Results The results of the water maze test revealed that the crossing numbers and the time spent in the target quadrant were significantly decreased in the 6-APP/PS1 and 12-APP/PS1 groups compared with the blank control group of the same age (all P < 0.05), whereas the 12-APP/PS1 group showed a more significant decrease than the 6-APP/PS1 group (both P < 0.05). Compared with the non-MEM group, the two parameters of the MEM treatment groups increased significantly (all P < 0.05). Histopathological observation showed that, compared with the age-matched blank group, the nerve cells in the olfactory bulb had no obvious atrophy and deformation, and the number of mitral cells was significantly reduced in the 6-APP/PS1 group (P < 0.05), while the nerve cells in the olfactory bulb were atrophic and deformed, and the number of periglomerular cells and mitral cells were significantly reduced in the 12-APP/PS1 group (all P < 0.05). Compared with the non-MEM group, the number of mitral cells were significantly increased in the 6-APP/PS1 group (P < 0.05), but there was no significant difference in the number of periglomerular cells and mitral cells in the 12-MEM group (all P > 0.05). Ultrastructural observation showed that, compared with the blank control group, the synaptic structure was swollen in the 6-APP/PS1 and 12-APP/PS1 groups, the thickness of the postsynaptic density was reduced and the number of asymmetric synapses decreased in the 6-APP/PS1 group, while the thickness of the postsynaptic density and the number of asymmetric synapses could not be observed clearly in the 12-APP/PS1 group. Compared with the non-MEM group, the synaptic swelling in the 6-MEM group was significantly improved, the thickness of the postsynaptic density and the number of asymmetric synapses increased, but the synaptic swelling in the 12-MEM group was not significantly improved, and the thickness of the postsynaptic density and the number of asymmetric synapses could not be observed.Conclusion Changes in the pathology and synaptic ultrastructural morphology of the olfactory bulbs in the APP/PS1 mice correlated with age, accompanied by behavioral alterations. MEM intervention not only improved spatial memory ability in the APP/PS1 mice, but also increased the number of mitral cells and alleviated the damage to the synaptic structure in the 6-APP/PS1 group, with significant improvement in early intervention.

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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
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    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.

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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
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    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.

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    A Novel Model for in-vivo Training of Postgraduates on Cardiac Electrical Conduction System Mapping Skills
    Xiaokang WANG, Ruojin ZHAO, Yunhui LÜ, Guangxin YUE, Shangyu LIU, Ting HE, Peng PENG, Liang MENG, Jubo LI, Baojie ZHANG, Chen SHEN, Yongchun CUI, Xin WANG
    Laboratory Animal and Comparative Medicine    2022, 42 (5): 466-471.   DOI: 10.12300/j.issn.1674-5817.2022.059
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    Objective StandardizationTo explore a novel special technique intensive mode (STIM) of teaching cardiac conduction system mapping skills. This method includes theoretical lecture, in vivo operation, 5-whys methods of analyses, intensive-problem oriented trainings, and assessments. Methods Ten post-graduates majoring in cardiology who have equivalent education backgrounds and technical levels were randomly divided into two groups (n=5 per group). All participants underwent a skill training on cardiac electrophysiology mapping, with one group training under the STIM and the other group under the traditional "theory-practice-test" (TPT) mode. The effect of these two educational techniques were evaluated at the end of the training. Results Postgraduates in the STIM group had a more solid grasp of the anatomical position and structure of the cardiac conduction system than those in the TPT group. During in-vivo operation, the students in the STIM group reconstructed and interpreted the electroanatomical maps, voltage maps, electric excitation maps, and electric conduction maps more accurately and quickly than those in the TPT group. Conclusion The STIM teaching mode more effectively improved the basic surgical skills of postgraduates, stimulated the students' learning initiative, and improved the quality of education. STIM is a kind of intensive teaching mode of special skills, and is worth widely implementing in the education of postgraduates majoring in cardiovascular diseases.

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    Research Progress on Mechanism and Intervention of Renal Function Injury in Hyperlipidemia Animal Model
    Xiaoli ZHOU, Qian ZHANG, Zhiyong QIAN
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 213-219.   DOI: 10.12300/j.issn.1674-5817.2021.116
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    Hyperlipidemia is closely related to renal function damage, and they influence each other. Lipid deposition in the kidney affects the function and structure of glomerulus and renal tubules directly and indirectly, resulting in renal function injury. On the contrary, renal function damage further affects lipid metabolism and aggravates the progress of hyperlipidemia. At present, besides synthetic drugs, there are many non-synthetic drugs which have been well verified in the intervention of kidney injury in hyperlipidemia animal model. In this paper, the research progress in the mechanism of renal function damage and the related intervention using hyperlipidemia animal model at home and abroad in recent years were summarized.

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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
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    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.

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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
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    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.

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    Analysis on the Standardized Expression of the Accredited Ability Scope for Hematology, Blood Biochemistry and Urinalysis in Laboratory Animal Clinical Testing
    Jian WANG, Jin LU, Lingyun TAO, Hongkun FU, Cheng GAO, Baojin WU, Yao LI, Yufeng TAO
    Laboratory Animal and Comparative Medicine    2022, 42 (6): 511-517.   DOI: 10.12300/j.issn.1674-5817.2022.172
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    To improve the application of hematology and urine testing of laboratory animals, and the consistency and effectiveness of the on-site review in China, there is a need for further standardization of the expression of testing ability in this field. In addition, it promotes better understanding and acceptance of the China National Accreditation Service for Conformity Assessment (CNAS) recognized results by relevant parties. In this paper, the expression of the accredited competence scope in the domestic and international institutes of laboratory animal hematology, blood biochemistry, and urine analysis fields were analyzed and compared. This study provides the CNAS with recommendations to standardize the expression of accreditation ability. In addition, it provides a detailed theoretical reference for further improving the process of standardizing testing of laboratory animals in China.

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    Explanation and Elaboration for the ARRIVE Guidelines 2.0—Reporting Animal Research and In Vivo Experiments (Ⅳ)
    Xiaying LI, Yonglu TIAN, Xiaoyu LIU, Xuancheng LU, Guoyuan CHEN, Xiao LU, Yu BAI, Jing GAO, Yao LI, Yusheng WEI, Wanyong PANG, Yufeng TAO
    Laboratory Animal and Comparative Medicine    2023, 43 (6): 659-668.   DOI: 10.12300/j.issn.1674-5817.2023.142
    Abstract153)   HTML27)    PDF (1188KB)(346)       Save

    Improving the reproducibility of biomedical research results is a major challenge.Transparent and accurate reporting of the research process enables readers to 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 fourth part of the article includes the items 1-5 of ARRIVE 2.0 Recommended 11 section, which covers "Abstract" "Background" "Objectives" "Ethical statement" and "Housing and husbandry". 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.

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    Investigation and Discussion on the Standardization Work of Feeds for Laboratory Animals
    Jianbo LUO, Junhui LI, Jia ZHOU, Yong HE, Min FU
    Laboratory Animal and Comparative Medicine    2022, 42 (5): 458-465.   DOI: 10.12300/j.issn.1674-5817.2022.019
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    Standardization of laboratory animals is the basis for obtaining accurate and stable experimental data, drawing objective and reliable experimental conclusions. The standardization of laboratory animal feeds is an integral part of laboratory animal standardization and an important support to realize laboratory animal standardization. In this paper, we compared the historical process of laboratory animal feeds standardization at home and abroad, outlined the key problems existing in the current domestic work, and put forward targeted countermeasures in order to provide references for the standardization of laboratory animal feeds in China.

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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
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    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.

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    Compound Casson Syrup Alleviates Acute Chemical Liver Injury in Mice Caused by D-galactosamine
    ·Ablimiti Merika, ·Abibule Aishan, Shen SHI, ·Abdu-reyimu Abdu-salamu, ··Taleb Enivar
    Laboratory Animal and Comparative Medicine    2022, 42 (3): 194-200.   DOI: 10.12300/j.issn.1674-5817.2021.140
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    Objective To investigate the protective effect of compound Casson syrup on acute chemical liver injury induced by D-galactose in mice.Methods The chemical liver injury model was established by intraperitoneal injection of D-galactose 800 mg/kg. The experiment was divided into 6 groups, including normal control group, model control group, positive control group of Yanxiaodinar syrup, and compound Casson syrup low-dose, medium-dose and high-dose groups, with 8 rats in each group. After intragastric administration of compound Casson syrup (8 mL·kg-1·d-1) and Yanchaudinar syrup (12 mL·kg-1·d-1), the changes of serum biochemistry, liver function and immunological indexes of liver injury were detected, and the pathological changes of liver tissue were observed.Results Compared with the normal control group, the liver index of model group was increased (P < 0.05), suggesting liver injury. Compared with model group, serum biochemical and liver function indexes were decreased after treatment with compound Casson syrup (P < 0.05). Compared with normal control group, the activities of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in liver homogenate of model group were increased (P < 0.05), and the activity of superoxide dismutase (SOD) was significantly decreased (P < 0.01). Compared with model group, SOD activity in compound Casson syrup groups was increased (P < 0.05). HE staining showed the inflammatory cell infiltration, degeneration, necrosis and other pathological phenomena of mouse liver caused by D-galactose were reversed after Casson syrup treatment.Conclusion Compound Casson syrup can effectively relieve the liver injury induced by D-galactose, and has a certain protective effect on liver.

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    Effects of Probucol Formulations on Mesenteric Lymphatic Trans-port Efficiency and Pharmacokinetics in Rats
    Xiaorui ZHANG, Jing CAO, Qianqian WU, Jijun LIU, Guoyuan CHEN, Baojin WU
    Laboratory Animal and Comparative Medicine    2022, 42 (4): 275-283.   DOI: 10.12300/j.issn.1674-5817.2022.026
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    Objective To compare the effects of probucol olive oil and suspension formulations on the pharmacokinetics and mesenteric lymphatic transport in rats using an innovative mesenteric-jugular lymphatic duct assisted reflux model. Methods Twelve Sprague-Dawley (SD) rats were randomly divided into four groups: suspension preparation-jugular vein single cannulation group (H-JD group), suspension preparation-jugular vein and intestinal lymphatic double cannulation group (H-JCS group), olive oil preparation-jugular vein single cannulation group (G-JD group), olive oil preparation-jugular vein and intestinal lymphatic double cannulation group (G-JCS group). The concentrations of probucol in whole blood and lymph fluid of rats at different times were determined by liquid chromatography and tandem mass spectrometry (LC-MS/MS), and drug-time curves were drawn. The pharmacokinetic parameters, relativebioavailability (Frel) and percentage dose in lymph fluid were calculated. Results The drug-time curve of each group conformed to the non-compartmental model. The peak times (Tmax) of the H-JD group, H-JCS group, G-JD group, and G-JCS group were (11±12), (5±2), (13±9), and (19±9) h, respectively; the peak concentrations (Cmax) were (148±60), (207±137), (453±204), and (309±177) ng/mL, respectively; the areas under the curve (AUClast) were (3 210±885), (3 677±2 014), (12 360±6 629), and (8 080±3 064) h·ng·mL-1, respectively. The percentages of lymphatic fluid dose in the H-JCS and G-JCS groups were (1.29±0.50)% and (2.59±0.43)%. Compared with the H-JD group, the Frel of probucol in the G-JD group was (409±269)%; compared with the H-JCS group, the Frel of probucol in the G-JCS group was (309±256)%. Compared with the H-JD and H-JCS groups, the whole blood values of Cmax, Tmax, AUClast and percentage of lymphatic fluid probucol concentrations of the G-JD and the G-JCS groups were significantly increased (P<0.05). The AUClast of whole blood in the G-JD group was significantly higher than that in the G-JCS group (P<0.05), but there was no significant difference between the H-JD and H-JCS groups (P > 0.05). Conclusion Olive oil formulation can improve the ratio of probucol transport through mesenteric lymph as well as its bioavailability.

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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
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    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.

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