动物实验,CYP2E1基因 z-bo 2020-08-24 545

　　Objective: To use two heart-specific CYP2E1 mice to evaluate the cardiotoxicity of sibutramine, and to select a more sensitive animal model to evaluate the cardiotoxicity of the drug.

　　Method: 8 weeks old male Tg(+) mice, sTg(+) mice and wild-type C57BL/6 mice (WT) were randomly divided into 5 groups, each with 50 mice and each with 10 mice. Mice and vehicle control group (by drinking purified water gavage) and four experimental groups (50, 100, 150, 300 mg/kg sibutramine). Observe general symptoms and determine the survival period during treatment. Blood was collected and dissected 15 days after administration. Collect hearts and determine the blood biochemical heart damage index of each group of experimental mice: lactate dehydrogenase (LDH), creatine kinase (CK), and creatine. Kinase isoenzyme (CK-MB). Histochemical method was used to observe the expression of connexin 43 (CX43) in heart tissue.

　　Results: (1) Blood biochemical indicators showed that the doses of Tg(+) mice were 50 mg/kg and 100 mg/kg, respectively, which were significantly higher than those of WT mice (P\u003c0 0.05 or P\u003c0.01) ; At doses of 50, 100, and 150 mg/kg, Tg(+) mice were significantly higher than sTg(+) mice (P\u003c0.05 or P\u003c0). .01); and at a dose of 300 mg/kg, Tg(+) mice were significantly lower than WT and sTg(+) mice (P\u003c0.05 or P\u003c0.01) and sTg(+). Histopathological results showed that the mice had the least decrease (2), indicating that each treatment group of Tg(+) and WT mice showed signs of heart damage (3) The immunohistochemical staining results showed that as the dose increased, The expression of CX43 in the myocardial plate insert of the three types of mouse CX43, Tg(+), sTg(+) and WT, gradually decreased, and the staining color gradually became brighter. However, the decrease in the number of CX43 cardiomyocytes expressed in the inserted intervertebral disc and the lightening of the staining color from high to low were observed in Tg(+) mice, followed by WT mice and sTg(+) mice.

　　Conclusion: Tg(+) mice are a good cardiotoxicity protection model, but Tg(+) mice are more sensitive than WT mice in assessing the potential cardiotoxicity of drugs in some cases