Objective:To explore the protective effect mechanism of it in rats with type 2 diabetes mellitus.Method:Method: The rat model of type 2 diabetes mellitus was built by utilizing high fat diet with low-dose streptozocin(40 mg·kg-1).All the rats were randomly divided into five groups,involving normal control group,model group,low-dose oleanolic acid group(50mg·kg-1·d-1),high-dose oleanolic acid group(100 mg·kg-1·d-1)and Oleanolic acid group(normal rats only given oleanolic acid,100 mg·kg-1·d-1).We should observe the growth,eating and activity of rats for 6 weeks.In week 0,week 3,6 weeks,we made metabolism experiments to observe its food intake and urine output,took the blood from rats to detect the levels of blood glucose.At the 6th week,rats were sacrificed to acquire blood,organs of all rats.HE staining was used to evaluate the changes of structure of the kidney.Blood was used to detect the total cholesterol,triglyceride,LDL-C,HDL-C,Scr,BUN.Using western blotting method to detect related protein expression in the Kidney.Result:1.The results of fasting blood glucose showed that the level of FBG in diabetic rats in each group was significantly higher than that in the normal control group(P<0.05),and after 3weeks of intervention,compared with the model group,the fasting blood glucose level of diabetic rats in each group was significantly higher than that in the model group.The level of FBG decreased in both low dose group and high dose group of oleanolic acid,and the level of FBG in both groups decreased further after 6 weeks of administration(P<0.05)after 6weeks of administration,Oleanolic acid low dose group and high dose oleanolic acid group showed a downward trend in Oleanolic acid low dose group and high dose oleanolic acid group.The level of FBG in the oleanolic acid control group was not significantly different from that in the normal control group(P> 0.05),but there was no significant difference between the oleanolic acid control group and the normal control group(P> 0.05).2.HE staining showed that there were no traumatic changes in renal tissue,normal morphology,complete structure,no proliferation of Mesangial matrix and no significant thickening of basement membrane in normal control group and oleanolic acid control group.The glomerular volume,Mesangial matrix,capillary basement membrane thickeningand inflammatory cell infiltration were observed in the model group.Compared with the model group,the renal injury was improved in varying degrees after intervention with different doses of oleanolic acid.3.The results of lipid metabolism showed that the serum TC,TG and LDL-C in the model group were significantly higher than those in the normal control group,while the HDL-C in the model group was significantly lower than that in the model group.The disturbance of lipid metabolism in low and high dose oleanolic acid groups was improved in varying degrees,such as the decrease of serum TC,TG and LDL-C and the increase of HDL-C.There was no significant difference in TC,TG,LDL-C and HDL-C between oleanolic acid control group and normal control group.4.The results of renal function showed that the levels of serum Scr and BUN in the model group were significantly higher than those in the normal control group.Compared with the model group,the levels of Scr and BUN in the high dose group were significantly lower than those in the model group,and the levels of Scr and BUN in the low dose group were also lower than those in the model group.5.The results showed that the expression of TLR4 and NF-?B protein in the model group was significantly higher than that in the normal control group(P> 0.05).The results showed that the expression of inflammatory associated protein in the kidney tissue in the model group was significantly higher than that in the normal control group(P>0.05).The expression of TLR4 and NF-?B protein in kidney tissue decreased in low and high dose oleanolic acid groups,and the difference was statistically significant(P> 0.05).There was no significant difference in the expression of TLR4 and NF-?B protein between the oleanolic acid control group and the normal control group.Conclusion:Oleanolic acid can effectively reduce blood glucose and improve diabetes renal injury,this improvement action is probably correlation to that oleanolic acid improving the glycolipid metabolism disorder and renal inflammatory.This study provides a new experimental basis for oleanolic acid in the prevention and treatment of glucose and lipid metabolism disorder and renal tissue injury in type 2 diabetic rats. |