盐酸小檗碱对糖尿病大鼠胸主动脉内皮损伤的保护作用

Protective effect of berberine on aortic endothelial dysfunction in diabetic rats

目的探讨盐酸小檗碱对2型糖尿病血管内皮功能损伤的保护作用。方法采用小剂量链脲佐菌素腹腔注射加高脂饲料喂养的方法建立2型糖尿病大鼠模型。将模型动物随机分为模型组、盐酸小檗碱组,另设正常对照组以及正常盐酸小檗碱组。用药组灌胃给药8w后,做葡萄糖耐量实验;检测各组动物血清中空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、空腹血清胰岛素(FINS)的水平;检测血清中一氧化氮(NO)和超氧化物歧化酶(SOD)含量;免疫组织化学方法检测内皮型一氧化氮合酶(eNOS)的表达。结果与模型组比较,盐酸小檗碱治疗组FPG、TC、TG水平明显下降(P<0.05),血清胰岛素水平有所升高,但无显著性差异(P>0.05);盐酸小檗碱能明显提高糖尿病大鼠胰岛素敏感指数,同时提高大鼠对腹腔注射葡萄糖的耐受力,改善胰岛素抵抗(均P<0.01);盐酸小檗碱可显著降低糖尿病组大鼠血清中NO含量,提高SOD水平(P<0.05,P<0.01);显著降低胸主动脉组织eNOS蛋白表达(P<0.05);而正常大鼠给予盐酸小檗碱治疗,上述指标未出现明显改变。结论盐酸小檗碱对2型糖尿病大鼠血管内皮损伤具有明显的保护作用。

Objective To observe the effect of berberine on serum NO level, SOD activity and eNOS expressions of aorta in type 2 diabetic rats induced by high fat diet plus STZ and explore the mechanism underlying protective effect of berberine on endothelial dysfunc- tion. Methods Wistar rats were randomly divided into diabetic, control, diabetic rats treated with berberine （ 100 mg/kg）, and control rats treated with berberine groups. After treatment, intraperitoneal glucose tolerance test（IPGTT） was performed. The serum fasting blood glucose, insulin, total cholesterol and triglyceride levels were tested, and insulin sensitivity index was calculated. The serum NO level and SOD activity were measured. In addition, eNOS protein expression was measured by immunohistochemical methods. Results Berberine signifi- cantly decreased fasting blood glucose, total cholesterol, triglyceride levels in diabetic rats. Berberine treatment also improved IPGTT in diabetic rats and enhanced tissue sensitivity to insulin. After berberine treatment, serum NO level and SOD activity were increased. Immunohis- tochemical results showed that berberine increased eNOS expression in diabetic rats aorta. Conclusions Berberine ameliorates diabetic endothelial dysfunction through decreasing blood glucose, lipid, improving insulin resistant, antioxidant effect and enhancing NO bioavailability.