动物造模,非酒精性脂肪性肝炎模型 z-bio 2021-02-25 364

　　OBJECTIVE: To investigate the inhibitory effect of telmisartan on the SOCS-3 pathway in the liver tissue of non-alcoholic steatohepatitis rats induced by high-fat diet and its intervention on insulin resistance.

　　Method: 70 male SD rats were randomly divided into group A (20 rats, normal control group), group B (30 rats, model control group) and group C (20 rats, experimental intervention). Rats in group A received a normal diet, and groups B and C received a high-fat diet. At the end of the 12th week, 10 rats in group B were randomly treated and tested positive for glucose and high insulin clamp tests. After the successful IR-NASH model (100%) was determined, groups B and C continued to be fed high-fat, and rats in group C received oral telmisartan 5 mg/kg daily. At the end of the 16th week (FBG), serum IL-6, TG, TC, ALT, AST and fasting blood glucose were measured in all rats to calculate serum insulin (FBI), insulin resistance index; positive glucose hyperinsulinemic clamp In the experiment, liver tissue HE liver pathology, semi-quantitative RT-PCR method was used to detect the expression level of SOCS-3 and SREBP-1 cmRNA in liver tissue.

　　Result: 12-week high-fat diet rats developed NASH. At the end of the 16th week, the wet liver weight of group B was significantly higher than that of group A, and group C was significantly lower than that of group B; group B had abnormal blood lipids, IR and serum IL-6 levels increased. developed. , Liver SOCS-3 mRNA and SREBP-1 cmRNA were significantly increased (compared with group A, P \u003cu003c0.01), and three of them were significantly negatively correlated with steady-state glucose infusion rate (VGIR60-120). 0.9248, P\u003c0.0001; = 0.9011, P\u003c0.0001; = 0.9739, P\u003c0.0001). After the intervention of Telmisartan, liver function and dyslipidemia were significantly improved, and the pathology of NASH was significantly improved. Compared with group B, SOCS-3 mRNA and SREBP-1 cmNA were significantly down-regulated (P\u003c0.01), while VGIR60-120 was significantly increased. (R = 0.9532, P\u003c0.0001; = 0.9687, P\u003c0.0001), showing a significant improvement in IR; IL-6 is still at a high level at this time, but VGIR60-120, SOCS-3 loss is related to SREBP-1c (R = 0.0071, P = 0.7238; = 0.0019, P = 0.8560; = 0.0002, P = 0.9586), SOCS-3 mRNA and SREBP-1 cmRNA are still significantly correlated (R = 0.9439, P\u003c0.0001).

　　Conclusion: Telmisartan intervention in NASH rats may significantly reduce and improve liver function and IR. The mechanism is to down-regulate the expression of SOCS-3 and SREBP-1c in the liver, instead of inhibiting the inflammatory factor IL-6, improving glucose and lipid metabolism and NASH.