熊果酸对糖尿病小鼠肝损伤的作用及其可能机制

目的：研究熊果酸对高脂饲料联合链脲佐菌素（STZ）诱导的糖尿病小鼠肝损伤的影响，探讨其可能的作用机制。方法：随机选取20只小鼠高脂饲料喂养6周后，STZ （30 mg/kg）腹腔注射连续5 d，9 d后测空腹血糖，大于11.1 mmol/L视为糖尿病模型，将其随机分为模型组和熊果酸组（100 mg/kg）（n=10）；另取10只小鼠设为对照组。连续给药8周。小鼠称重，测定空腹血糖（FBG），血清总胆固醇（TC）、甘油三酯（TG）含量，谷丙转氨酶（ALT）、谷草转氨酶（AST）、超氧化物歧化酶（SOD）活性，丙二醛（MDA）含量，HE染色观察肝组织病理变化。结果：模型组与对照组比较，FBG、血清TC、TG含量，ALT、AST活性、MDA含量明显升高（P<0.05，P<0.01）；SOD活性明显降低（P<0.01）；HE染色显示部分肝细胞水肿，轻度脂肪变性，门管区可见淋巴细胞浸润。熊果酸组与模型组比较，FBG，血清TC、TG含量，ALT、AST活性、MDA含量明显降低（P<0.05，P<0.01）；SOD活性明显升高（P<0.01）；HE染色显示熊果酸组肝细胞排列较为整齐，水肿不明显，淋巴细胞少量存在。结论：熊果酸对高脂饲料联合STZ诱导的糖尿病小鼠肝损伤具有保护作用，其机制可能与降血糖、调节血脂、降低肝组织氧化应激水平，提高肝脏抗氧化能力有关。

Effects of ursolic acid on liver injury and its possible mechanism in diabetes mellitus mice

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.