阻断肾素-血管紧张素系统对糖尿病大鼠肾脏蛋白激酶CβⅡ亚型的影响

Action of blocking renin-angiotensin system on protein kinase CβⅡ isoform in renal tissue of diabetic rats

目的 研究链脲佐菌素诱导的糖尿病大鼠肾组织蛋白激酶C(PKC) βⅡ亚型的表达和转位 ,以及阻断肾素 血管紧张素系统 (RAS)对其的影响。方法 糖尿病模型大鼠随机分为伊贝沙坦组 (4 0mg·kg-1·d-1)、福辛普利组 (4 0mg·kg-1·d-1)、两药合用组 (各 2 0mg·kg-1·d-1)、糖尿病对照组。另设正常对照组。给药 4周末检测各组血糖、胰岛素水平 ,采用免疫组化法检测肾组织中PKCβⅡ的表达 ,Western印迹法检测肾皮质、髓质PKCβⅡ的表达和胞膜转位情况。结果 糖尿病对照组肾皮质总的和胞膜部分的PKCβⅡ表达量均明显降低 ,分别为正常对照组的 66.0 %和 5 0 .0 % (均P <0 .0 5 ) ,而各治疗组均可部分地纠正这种异常。肾髓质各组间PKCβⅡ的总量及胞膜、胞浆部分的量差异无显著性。结论 早期糖尿病大鼠肾脏中PKCβⅡ的表达存在着量和转位的异常 ,而阻断RAS可部分纠正这种变化 ,提示RAS可通过影响PKC转导途径的异常而参与糖尿病肾病的发生发展机制。

Objective To investigate the expression and translocation of protein kinase C (PKC) βⅡ isoform in renal tissue of diabetic rats and the effects of blocking renin-angiotensin system (RAS) on them. Methods Diabetic rats induced with streptozotocin were randomized to 4 groups. (1) Diabetic control without treatment. (2) Treatment with irbesartan (40 mg·kg -1 ·d -1 ). (3)Treatment with fosinopril (40 mg·kg -1 ·d -1 ) and (4) Treatment with a combination of irbesartan and fosinopril (20 mg·kg -1 ·d -1 each). Six normoglycemic rats served as normal control. After 4 weeks, blood glucose and insulin were measured and expression and translocation of PKCβⅡ in renal cortex and medulla were assessed by immunohistochemistry and Western blot. Results The expressions of total and membrane fraction in renal cortex of diabetic control rats weredecreasedto66.0%and50.0% of the values of normal control rats respectively (both P<0.05). Treatments with irbesartan, fosinopril and their combination partially corrected the above abnormalities. The expressions of PKCβⅡ in the membrane and cytosol fractions from medulla showed no diffe-rence among 5 groups. Conclusion In diabetic rats, decreased expression of PKCβⅡ in renal cortex could be partially corrected by treatment with irbesartan, fosinopril and their combination. These results suggest that RAS was implicated in the pathogenesis of diabetic nephropathy by regulating the expression and activation of the PKCβⅡ isoform in diabetes.