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    25 February 2021, Volume 41 Issue 1
    40th Anniversary Expert Forum
    Development Trend and Challenge of Comparative Medicine from Human Genome Project to Precision Medicine
    ZHAO Guoping
    2021, 41(1):  1-8.  DOI: 10.12300/j.issn.1674-5817.2021.022
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    By reviewing the development from human genome project to precision medicine, we can have a more comprehensive and accurate understanding on comparative medicine, thus provide important enlightenment for more precise and efficient comparative medicine research. Starting from the development from human genome project to precision medicine, this paper summarized and analyzed the development trend of comparative medicine, that is, humanization of laboratory animals and personification of animal models. Moreover, the paper pointed out that under the challenge of big data era, comparative medicine research should play its “cross convergence” characteristics, achieve breakthroughs in research methods and technologies, and improve the efficiency and quality of human health research.
    40th A nniversary: Development of I aboratory A nimal Science A cross China
    Development of Shaanxi Laboratory Animal Science in Past 10 Years
    SHI Changhong, LIU Enqi, ZHANG Hai
    2021, 41(1):  14-16.  DOI: 10.12300/j.issn.1674-5817.2021.011
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    40th Anniversary: Development of the Journal
    Original Article: Animal Models of Human Diseases
    Changes and Significance of Arterial Blood Gas Analysis Indexes in Rats with Chronic Hypoxic Pulmonary Hypertension
    ZHANG Shuting, YAO Qingqing, LI Yishan, SHI Yiwei
    2021, 41(1):  27-32.  DOI: 10.12300/j.issn.1674-5817.2020.080
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    Objective To investigate the changes and significance of arterial blood gas analysis indexes in a rat model of pulmonary hypertension induced by chronic hypoxia. Methods Thirty-six SD male rats were randomly divided into the normoxic control group and the hypoxic groups. The rats in the hypoxic groups were placed in a hypoxic chamber (10% oxygen concentration) for 1, 3, 7, 14, 21 days, respectively. Right ventricular systolic pressure (RVSP) was measured by right ventricular catheter, and right ventricular hypertrophy index (RVHI) was calculated by calculating the weight ratio of right ventricle (RV) to [left ventricle (LV) + ventricular septum (S)]. Masson staining was used to observe the pathological changes of pulmonary artery. Blood was taken from the abdominal aorta for the arterial blood gas analysis to determine the following indexes: pondus hydrogenii (pH), arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2), bicarbonate (HCO3), sodium (Na+), potassium (K+), calcium (Ca2+), hematocrit (Hct) and hemoglobin (Hb). Results RVSP and RVHI of the rats were significantly increased in the hypoxic groups compared with the normoxic control group (P<0.05). Compared with the normoxic control group, the hypoxic groups (7, 14, 21 days) had abnormal pulmonary artery remodeling. Compared with the normoxic control group, the pH and HCO3 levels of the hypoxic groups were significantly reduced (P<0.05); PaCO2 level was significantly increased in the hypoxic 21-day group (P<0.05), PaO2 and SaO2 levels were significantly decreased in the hypoxic 14-day group (P<0.05), the Na+ concentration (except hypoxia 1-day group) and the Ca2+ concentration (hypoxic 3-day group) were significantly reduced (P<0.05); the K+ concentrations were increased significantly in the hypoxic groups (except hypoxia 14-day group) (P<0.05); Hct and Hb were significantly increased in the hypoxic groups (P<0.05). There was a significant negative correlation between Na+ and RVSP in rats with hypoxic pulmonary hypertension (P<0.05). Conclusion The arterial blood gas analysis indexes, including pH, PaCO2, PaO2, SaO2, HCO3, Na+, K+, Ca2+, Hct and Hb are significantly changed, and participate in and regulate the development and progression of hypoxic pulmonary hypertension in rats, in which Na+ level may be used as an indicator to evaluate the severity of hypoxic pulmonary hypertension indirectly.
    Establishment of Ulcerative Colitis Model in Mice by Different Drug Delivery Methods of Dextran Sodium Sulfate
    ZHAO Yani, LI Yao, ZHANG Yan, WANG Siwang, AN Junming
    2021, 41(1):  33-39.  DOI: 10.12300/j.issn.1674-5817.2020.090
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    Objective To study the modeling situation of ulcerative colitis in mice by gavage or free drinking of dextran sulfate sodium (DSS) respectively. Methods Thirty two male C57BL/6 mice were randomly divided into a blank control group, a 3% DSS free drinking group, 5 g/kg and 6 g/kg DSS gavage groups, with eight mice in each group. The drug treatments lasted for 7 days. The water intake, body weight, stool characteristics and hematochezia of mice in each group were recorded daily, and the disease activity index (DAI) score of mice was calculated daily. After the mice were sacrificed on the 8th day, the colon, thymus and spleen were separated, the thymus and spleen were weighed, and the immune organ index was calculated; the colon was measured for length and observed for pathological changes, and the histopathological score was assessed. Results The total intake of DSS in each administration group exceeded 30 mg/g for 7 days. Compared with the blank control group, there was no significant difference in the DAI score of mice in the gavage groups (P>0.05), and the DAI score of mice in the free drinking group increased significantly from the 3rd day (P<0.01). Compared with the blank control group, the colon of mice in each administration group was shortened (P<0.01), but the thymus index showed no significant difference (P>0.05). The decreasing of thymus index and colon atrophy of mice in the free drinking group were more significant than those in the gavage groups (P<0.05). In terms of histopathological changes, the mice in the 6 g/kg gavage group had slight pathological changes, and the mice in the free drinking group had more significant pathological changes, and the histopathological score in the free drinking group was significantly higher than those in the gavage groups (P<0.01 or P<0.05). Conclusion When DSS is used to establish the model of ulcerative colitis in mice, the free drinking method is more effective than the gavage administration.
    Preliminary Probing for Reproductive Performance in Female Dwarfism Rats
    JIAO Shufan, XU Longmei, HUA Zhengyu, YAO Jufang
    2021, 41(1):  40-45.  DOI: 10.12300/j.issn.1674-5817.2020.166
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    Objective To probe the causes of low reproductive performance in spontaneous dwarfism Wistar rats (SDWR). Methods A Wistar rat control group and a SDWR group both included 50 female and 50 male rats aged 12 weeks respectively, and were mated 1∶1 (male to female); the pregnancy rate, litter size, litter birth weight, weaning rate and weaning weight of the SDWR and Wistar rats were measured from the first parity to the fourth. Twenty female SDWR aged 8 weeks and 20 female Wistar rats aged 5 weeks were selected respectively to evaluate puberty and estrous cycle by vaginal cytology. Twenty female SDWR and 20 female Wistar rats aged 6-8 weeks were respectively injected intraperitoneally with 200 U/kg, 300 U/kg and 400 U/kg of pregnant mare serum gonadotropin (PMSG) plus human chorionic gonadotropin (hCG) for superovulation, and the ovulation induction effects. Twenty Wistar, 20 SDWR and 20 SDWR superovulation rats aged 6-8 weeks were compared in morphological changes of ovarian tissue by HE staining. Results The pregnancy rate, litter size, litter birth weight, weaning weight and weaning rate of the first parity to the fourth of the SDWR group were significantly lower than those of the Wistar group (P<0.05). In the SDWR group, sexual maturation [(12.15 ± 0.81) weeks] was significantly delayed compared with the Wistar group [(8.05±0.76) weeks]. The Wistar group maintained a regular estrous cycle of 4-5 days, while the SDWR group showed an extended and disordered estrous cycle of 7-8 days, shortened estrous and extended metestrus. The results of superovulation test showed that the number of eggs in the SDWR group was significantly lower than that in the Wistar group (P<0.01). The results of HE staining of ovarian tissue showed that in the Wistar group, follicles at all levels were growing actively, and granular cells and corpus luteum structure were normal; while in the SDWR group, the number of total ovarian follicles and follicles at all levels were significantly reduced, and granular cells was disarranged. Conclusion The low reproductive rate of SDWR may be related to delayed sexual maturity, prolonged and disordered estrous cycle, and ovarian dysfunction.
    Original Article: Laboratory Animal and Traditional Chinese Medicine
    Safety Pharmacology Evaluation of Tanreqing Injection by Animal Experiment
    HU Jun, ZHANG Xiaoli, YANG Chun, LU Jinyao, WANG Qiong, GU Yingmin, XIE Jiajun, ZHANG Chaochao, TIAN Xuesong
    2021, 41(1):  46-54.  DOI: 10.12300/j.issn.1674-5817.2020.068
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    Objective To observe the effects of Tanreqing injection on the cardiovascular and respiratory systems in Beagle dogs and the central nervous system in ICR mice, and to provide the animal safety data for its clinical application. Methods A total of 24 Beagle dogs (12 males and 12 females) were randomly divided into low dose (2.5 mL stock solution/kg), medium dose (5 mL stock solution/kg), high dose (10 mL stock solution/kg) Tanreqing injection groups and a solvent control group according to their body weight; there were 6 dogs in each group with intravenous injection at the right cephalic vein of forelimb under anesthesia. Then the blood pressure, heart rate, electrocardiogram and respiration rate were measured before, during at 40 and 80 min, as well as 5, 10, 20, 30, 60, 90, 120, 150, 180, 210 and 240 min after administration of Tanreqing injection. A total of 160 ICR mice (half male and female) were selected, and 60 of them were randomly divided into low dose (3.6 mL stock solution/kg), medium dose (6.25 mL stock solution/kg), high dose (12.5 mL stock solution/kg) Tanreqing injection groups, a solvent control and a positive control groups according to their weight, and their general behavior and spontaneous activity were recorded after different doses of Tanreqing injection via the tail vein. The coordinated movement of other 50 mice with the same grouping method were measured at different time points after administration of Tanreqing injection. The synergistic effect of pentobarbital sodium hypnosis at subliminal dosage was tested in the rest of 50 mice with the same grouping method. Results Compared with the solvent control group at the same time point or the group itself before administration, there were no significant differences in systolic pressure, mean arterial pressure, electrocardiogram and respiration rate (all P>0.05) of the Beagle dogs in the Tanreqing injection groups at different doses; while the diastolic pressure and heart rate at some time points were statistically significant (P<0.05 or P<0.01), but there was no dose or time dependent effect. The spontaneous activity of the ICR mice was decreased at each time point (P<0.05, P<0.01 or P<0.001), and the oordinated movement grades were increased at 30, 50 and 90 min after high-dose Tanreqing administration (P<0.05, P<0.01 or P<0.001). Conclusion No significant effects of Tanreqing injection on the cardiovascular and respiratory systems of Beagle dogs are found after single intravenous injection in this experiment. High-dose Tanreqing injection has certain effects on the central nervous system of mice, mainly reduced spontaneous activity and in coordinated movement, which may be related to bear bile powder, the main active ingredient of Tanreqing injection.
    Mechanism of Protective Effect of Raddeanin A on Hepatic Ischemia-reperfusion in Rats
    LI Hongbo, HUANG Rui, DAI Jiang, ZHONG Zhendong
    2021, 41(1):  55-60.  DOI: 10.12300/j.issn.1674-5817.2020.077
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    Objective To explore the protective mechanism of raddeanin A (RA) on hepatic ischemia-reperfusion injury in rats. Methods Thirty rats were randomly assigned into three groups including sham, model and RA groups (n=10). The rats in the RA group were injected with RA (10 mg/kg) in the tail vein 24 h and 1 h before model construction. The rats in the sham and model groups were injected with normal saline of equal volume. After the rats were anesthetized, the blood vessels entering the liver were blocked for 60 min, causing 70% of the liver to be ischemia. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in serum were detected 6 h after liver blood flow was restored, the superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1? (IL-1?), interleukin-6 (IL-6) and tumor necrosis factor-〈 (TNF-〈) levels in liver were detected by ELISA. Liver specimens were stained with hematoxylin-eosin (HE) and TUNEL for observation of pathologic and apoptotic changes. Bcl2-associated X protein (Bax), Bcl-2 and Caspase-3 protein levels in liver were detected by Western blotting. Results The levels of ALT, AST and LDH in the RA groups were lower than those in the model group (P<0.01). The levels of MDA, IL-1b, IL-6, TNF-a, Bax and Caspase-3 in the RA groups were lower than those in the model group (P<0.05), the levels of SOD and Bcl-2 were higher (P<0.05). The structure of hepatic lobules was complete in the RA group. The apoptotic cells and the apoptosis rate in the RA group were lower than those in the model group (P<0.01). Conclusion Preoperative injection of RA can protect the liver by improving the liver function of rats after ischemia-reperfusion, reducing the release of oxidative and inflammatory factors, and reducing the apoptosis of hepatocytes via down-regulating the expressions of Bax and Caspase-3 proteins.
    Laboratory Animal M lanagement
    Application of Experimental Material Inspection in Quality Control of SPF Mice
    CHEN Guoyuan, KANG Kang, LI Xiaoxian, JI Wentao, ZHANG Jinmei, FENG Yanhua, TIAN Qianying, WU Baojin
    2021, 41(1):  61-65.  DOI: 10.12300/j.issn.1674-5817.2020.092
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    Objective To establish inspection methods for materials carried into barrier facilities housing specific pathogen-free (SPF) laboratory mice. Methods Experimental materials brought into a murine barrier facility were collected. Non-cellular material samples were cultured to identify whether samples harbored bacteria, and cell samples were screened for the presence or absence of mycoplasma using PCR. Results A total of 14 708 experimental materials were collected and evaluated over a 5-year period. The average positive rate for bacterial detection in 13 085 non-cellular samples was 1.99%, and the positive rate for mycoplasma in 1 623 cell samples was 4.81%. Positive detection rates for bacteria and mycoplasma have gradually decreased and have remained at low levels over recent years. Conclusion sIt is feasible to conduct continuous large-scale inspection, monitoring, and control of experimental materials used in animal barrier facilities. Inspection processes can strengthen the confidence of researchers performing aseptic treatment with animal experimental materials and enable facility managers to evaluate risks from experimental materials. Experimental material inspection is an effective measure for microbial quality control in SPF experimental mice.
    Design of Health Code Management Framework for Laboratory Animals
    JIANG Kun, TANG Yiwen, LIU Yanbin, CHEN Liming, TANG Hongbin
    2021, 41(1):  66-69.  DOI: 10.12300/j.issn.1674-5817.2020.075
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    Health code is a form of two-dimensional electronic certificate with personal real data. It can greatly improve management efficiency when applied to the supervision of administrative licenses involving laboratory animals in the process of production, transportation, and use. According to the characteristics of provincial territorial management of laboratory animals, a unified information interface standard should be established to realize national mutual recognition for promoting industrial circulation. This would represent a development trend under 5G conditions such that network management of laboratory animals on the fixed end is transformed into information management of laboratory animals on mobile handsets.
    Review
    Metabolic Disease Animal Models induced by High-fat Diets
    LUO Jianbo, LI Junhui, WANG Haijiang, ZHOU Xiaoyu, ZENG Tao, ZHOU Jia, ZHU Xianjun
    2021, 41(1):  70-78.  DOI: 10.12300/j.issn.1674-5817.2021.050
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    High-fat diets are often used to induce models with nutritional abnormalities and stimulate human diseases, which are used to explore the mechanism of disease development and widely used in clinical hypothesis study. In order to provide theoretical and practical basis for researchers in this field, recent advances on animal models of metabolic diseases induced by high-fat diets were reviewed, and the mechanisms underlying disease development and the respective roles of nutrient components of the diets were also discussed.