胰岛素、卡托普利对糖尿病大鼠肾小球蛋白激酶C同工酶表达变化的影响  

Effect of insulin and captopril on the expression of protein kinase C isoforms in diabetic rat glomerulus

作　　者：姚丽[1] 王力宁[1] 范秋灵[1] 冯江敏[1] 马健飞[1] 

机构地区：[1]中国医科大学附属第一医院血液净化中心,辽宁沈阳110001

出　　处：《中国现代医学杂志》2007年第1期59-62,共4页China Journal of Modern Medicine

摘　　要：目的探讨胰岛素、卡托普利对糖尿病(DM)大鼠不同阶段肾小球蛋白激酶C(PKC)同工酶表达变化的影响及其对糖尿病肾病的保护作用。方法将实验动物随机分为STZ-DM模型组、胰岛素治疗组及卡托普利治疗组2、4和12周,采用免疫组化方法检测PKC同工酶在肾小球细胞的表达变化情况。结果胰岛素治疗使DM大鼠的高血糖和多尿得到明显控制,并使已经升高的内生肌酐清除率(Ccr)显著下降,减轻了肾重/体重的增加。卡托普利治疗12周显著降低了DM大鼠尿蛋白排泄率和肾重/体重。在肾小球细胞内,PKCα在DM发病2、4和12周时表达显著上升(P<0.05);PKCβⅡ在DM发病2周时表达明显下降(P<0.05),4和12周时恢复正常。胰岛素、卡托普利明显抑制了2和4周组DM大鼠肾小球PKCα的表达以及4周组DM大鼠PKCβ2的表达(P<0.05);卡托普利使12周组DM大鼠肾小球PKCα、PKCβ2表达明显下降(P<0.05)。结论胰岛素、卡托普利通过调节DM大鼠肾小球细胞PKCα和PKCβ2表达延缓糖尿病肾病(DN)的发生、发展。[Objective] To investigate the effect of insulin and captopril on the expression of protein kinase C isoforms in diabetic rat glomerulus and evaluate the influence of insulin and captopril on the development of diabetic nephropathy. [Methods] The animals were divided into diabetic group, insulin treatment group and captopril treatment group at random. Hyperglycemia was induced by streptozotocin （STZ, 60 mg/kg） in the male Sprague-Dawley rats （body weight 150-170 g）. Diabetes was confirmed by blood glucose ≥ 13.9 mmol/L two day after STZ administration. Age-matched normal rats received 3 mg/kg bw 0.9% saline, and served as control group. Insulin is injected by subcutaneous to control blood glucose below 11.1mmol/L at the dosage of 8-40 u and captopril is taken orally with water at the dosage of 50 mg/kg. Rats 2 weeks, 4 weeks and 12 weeks after the onset of hyperglycemia and treatment by insulin or captopril were anesthetized with 50 mg/kg of intraperitoneal sodium pentobarbital, and the kidneys were rapidly removed. The expression of PKC isoforms in normal and diabetic glomerulus was assessed by immunohistochemistry. [Results] Treatment with insulin decreases hyperglycemia, urine volume, kidney weight/body weight and endogenous creatinine clearance in diabetic rats. Captopril treatment for 12 weeks reduces urinary prorein excretion and kidney weight/body weight in diabetic rats. Immunohistochemistry revealed a significant increase in the expression of PKCα in glomerular ceils at 2 weeks, 4 weeks and 12 weeks after hyperglycemia was induced （P 〈0.05）; PKC β2 showed a significant decrease in the glomerular cells at 2 weeks after hyperglycemia and a gradually increase to normal level at 4 weeks and 12 weeks. The increases in PKCot and PKCβ2： expression were decreased by treatment with insulin or captopril （P 〈0.05）. [Conclusion] Treatment with insulin and captopril delay the onset and development of diabetic nephropathy through modulating the expression of PKCot and PKC β2 in glomerular c

关 键 词：胰岛素 卡托普利 蛋白激酶C同工酶 肾小球 糖尿病肾病 

分 类 号：R-332[医药卫生]