| background: Type 2 diabetes is often associated with non-alcoholic fatty liver disease(NAFLD).Excessive accumulation of fat in the liver in the form of triglyceride(TG)causes hepatic steatosis.Its incidence is about 30% in the general population,and it has increased about 3 times in patients with type 2 diabetes.The main characteristics of type 2 diabetes mellitus with nonalcoholic fatty liver disease are: disorder of glucose and lipid metabolism,especially in fasting blood glucose and triglyceride.The increase in fasting blood glucose is caused by increased gluconeogenesis of the liver.Studies have shown that the rate of gluconeogenesis in patients with NAFLD has increased by 30%.Object: This experiment mainly explore the effect of oleanolic acid on SIK1/SREBP-1c to improve fatty liver and glycolipid metabolism of rats with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease.Method: In this experiment,Wistar rats were continuously fed with high-fat diets for 4 weeks and injected with low-dose(35mg/kg)streptozotocin to form rats with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease.Rats in the oleanolic acid group were orally administered 30 mg /(kg · d)of oleanolic acid tablets,and the rats of the metformin group were orally administered 140 mg /(kg · d).Orbital venous blood was taken from rats to dete ct related biochemical indicators.The pathological changes of liver were observed by HE staining.The expression of SIK1 and SREBP-1c was detected by RT-PCR and Western Blot.Results: In the DM group,FBG,TC,TG,ALT,AST and wet liver weight of rats were significantly higher than the normal control group(p <0.05),and the body weight was significantly lower than the normal control group(p <0.05).Compared with the diabetic group,the body weight of rats of the metformin group and the OA group were significantly improved(p <0.05).The liver weight of rats of the OA group and the metformin group were significantly reduced compared with the diabetic group(p <0.05).Compared with the DM group,the fasting blood glucose of rats of the OA group and the metformin group were significantly reduced(p <0.05);the total triglyceride was significantly reduced(p <0.05);ALT and AST were significantly reduced(p<0.05).The total cholesterol of rats of the oleanolic acid group was significantly lower than that in the DM group(p <0.05).HE staining results showed that the liver of the normal group had no obvious damage and fatty lesions,and the liver of the model group had severe fatty liver lesions.The liver of rats in the oleanolic acid group showed moderate fatty liver disease and the liver of in the metformin group showed moderate to severe fatty liver disease.RT-PCR results showed that the expression of SIK1 in liver of rats of DM group was significantly lower than that of normal control group,and the expression of SREBP-1c was significantly higher than that of normal control group(P <0.05).The expressions of SIK1 in liver of rats of metformin group and OA group were significantly higher than that of DM group,while the expression of SREBP-1c was significantly lower than that of DM group.Western Blot results showed that the expression of SIK1 in liver of rats of DM group was significantly lower than that of normal control group,while the expression of SREBP-1c was significantly higher than that of normal control group(P <0.05).The expression of SIK1 in liver of rats of metformin group and OA group were significantly higher than that of DM group,while the expression of SREBP-1c was significantly lower than that of DM group.Conclusion: 1.OA can effectively regulate the expression of SIK1/SREBP-1c to regulate lipid metabolism of rats with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease.OA can reduce liver damage and improve fatty liver disease.2.OA can effectively reduce fasting blood glucose of rats with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease to slow down the process of further complications caused by glucose toxicity. |
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