Abstract: Objective:To study the effects of ursolic acid on liver injury in diabetic mice induced by high-fat diet combined with streptozotocin(STZ), and to explore its possible mechanisms. Methods:Diabetes mellitus was induced in twenty male ICR mice by a combination of high-fat diet for 6 weeks with low-dose streptozotocin (30 mg/kg, i. p.) for 5 consecutive days. After 9 days, fasting blood glucose levels were determined. Mice with fasting blood glucose levels exceeded 11. 1 mmol/L were diagnosed as diabetic mice and selected for further experiment. These mice were randomly divided into two groups(each group of 10):diabetic group, ursolic acid group (100 mg/kg, i. g.), and another 10 mice were set as control group. After continuous administration for 8 weeks, body weight (BW) were weighed, fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate transaminase (AST) in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver were measured. HE staining was used to observe pathological changes of liver tissue. Results:Compared with the control group, the level of FBG, TC, TG, ALT, AST, MDA were dramatically increased (P<0. 05, P<0. 01) and SOD was markedly decreased (P<0.01) in the diabetic group; HE staining showed that parts of liver cells swelled and had a light fatty degeneration as well as lymphocyte infiltrated around the portal area in model group. Compared with the diabetic group, the level of FBG, TC, TG, ALT, AST, MDA were significantly declined (P<0.05, P<0.01) and SOD was considerably increased (P<0.01) in the ursolic acid group; HE staining showed that the liver cells relatively arranged in order, edema was not obvious and inflammatory cells infiltrated lightly in the ursolic acid group. Conclusion:Ursolic acid has a protective effect on liver injury in diabetic mice induced by high-fat diet combined with STZ by intraperitoneal ingector, and its mechanism may be associated with lowering blood glucose, regulating the lipid metabolism, reducing oxidative stress and enhancing the ability of anti-oxidation in liver.

Key words: ursolic acid, diabetic liver injury, oxidative stress, mice