厄贝沙坦对2型糖尿病大鼠肾脏氧化应激和蛋白激酶C活性的影响

Effect of Irbesartan on Oxidative Stress and the Activity of Protein Kinase C in Type 2 Diabetic Rats

目的 :探讨厄贝沙坦对 2型糖尿病大鼠肾脏氧化应激 (OS)和蛋白激酶C(PKC)活性的影响。方法 :将实验动物分为正常对照组、糖尿病组及厄贝沙坦治疗组。检测各组第 4 ,5 ,11,17周的血糖、血胰岛素、血脂 (TG、TC) ,11,17周的血肌酐 (Scr)、血尿素氮 (BUN)、尿微白蛋白排泄率 (UAE)、肾组织中丙二醛 (MDA)含量、铜 ,锌 超氧化物歧化酶 (Cu ,Zn SOD)、过氧化氢酶 (CAT)、谷胱甘肽过氧化酶 (GSH Px)及PKC活性。结果 :与糖尿病组相比 ,厄贝沙坦治疗组血糖、血胰岛素及血脂无明显变化。而Scr、BUN、UAE、肾脏MDA含量、肾细胞膜PKC均明显下降 ,肾脏抗氧化酶活性 (Cu ,Zn SOD、CAT、GSH Px)则明显上升。作相关性分析发现肾脏内MDA含量的变化及抗氧化酶活性的变化与细胞膜、细胞浆PKC活性的变化相关。结论 :厄贝沙坦可以抑制 2型糖尿病大鼠肾脏内的氧化应激 ,并且这种抑制作用与其下调蛋白激酶C活性有关。

Objective: To investigate the influence of irbesartan on oxidative stress and the activity of protein kinase C in type 2 diabetic rats. Methods: Tirty-six Wistar rats(male,160～180 g) were divided into three groups as normal group、diabetic group and diabetic group treated with irbesartan(50 mg·kg -1 ·d -1 ). Blood glucose, blood insulin and blood lipid were measured after 4,5,11 and 17 weeks of experiments. Serum creatinine,blood uria nitrogen,urinary albumin excretory rate, lipid peroxidation (MDA),the activity of protein kinase C (PKC) and of antioxidant enzymes including Cu,Zn superoxide dismutase(Cu,Zn-SOD),catalase (CAT) and glutathione peroxidase(GSH-Px) in renal tissue were measured at 11 and 17 week of experiments. Results: The blood glucose,blood insulin and blood lipid were found no significant difference between diabetic rats with or without irbesartan treatment. Compared to those of untreated group,the level of serum creatinine,blood uria nitrogen,urinary albumin excretory rate, renal MDA and the activity of cell membrane PKC in irbesartan treated group significantly decreased,but the activity of renal Cu,Zn-SOD,CAT and GSH-Px increased. In addi-tion,there was a correlation between renal MDA change and the change of cell membrane PKC activity. Conclusion: Irbesartan is effective in improving the state of oxidative stress in type 2 diabetic rats, and this is correlated with it′s role of decreasing the activity of cell membrane PKC.