建立大鼠糖尿病模型研究替米沙坦对大鼠肾脏内氧化应激的抑制作用及对其蛋白激酶C的影响

The Effects of Telmisartan on Oxidative stress and the Activity of Protein Kinase C in Type 2 Diabetic Rat

目的探讨替米沙坦对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、糖尿病组及替米沙坦治疗组。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,替米沙坦治疗组血糖、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。做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、细胞质PKC活性的变化相关。结论替米沙坦可以抑制2型糖尿病大鼠肾脏内的氧化应激,并且这种抑制作用可能与其下调蛋白激酶C活性有关。

Objective To observe the effets of telmisartan on oxidative stress and the activity of protein kinase C in type 2 diabetic Rat. Methods Thirty six Wistar rate were divided into three groups as normal rats.diabetic rats and diabetic rats treated with telmisartan. Blood glucose, blood insulin, blood lipid were measured after 4,5,11 and 17 weeks, serum creatinine, blood uria nitrogen, urinary albumin excretory rate, lipid peroxidation（ MDA）, the activity of protein kinase C （PKC） and of ant/oxidant enzymes including Cu/Zn superoxide dismutase（ Cu, Zn - SOD） ,catalase（CAT） and glutathione peroxidase（ GSH - Px） in renal tissue were measured after 11 and 17 weeks.In addition,the renal tissue were observed by light microscopy. Results The blood glucose and blood insulin were found no significant difference between that in type 2 diabetic rats with and without telmisartan treatment groups. Comparing with untreated group, the level of blood lipid ,serum creatinine ,blood uria nitrogen, urinary albumin excretory rate, renal MDA and the activity of cell membrane PKC in telmisartan treated group were significantly decreased, but the activity of renal Cu/Zn SOD, CAT and GSH -Px was increased. There was significant correlation between the change of renal MDA and the activity of antioxidase and the activity of cell membrane PKC. Conclusion Teimisartan could inhibit oxidative stress in diabetic rats, and its mechanism perhaps was decreasing the activity of cell membrane PKC.