苯那普利对糖尿病大鼠肾脏组织细胞膜胰岛素受体及其底物-1蛋白表达的影响

目的:研究血管紧张素转换酶抑制剂苯那普利对糖尿病大鼠肾脏组织细胞膜胰岛素受体(IR)及其底物-1(IRS-1)蛋白表达的影响。方法:实验大鼠随机分3组:对照组(n=6);糖尿病组(n=7)及糖尿病+苯那普利治疗组(n=7)。4周后观察各组体重、肾重及肾重/体重之比的变化,应用荧光分光光度法测定血浆、肾脏组织血管紧张素转换酶(ACE)活性,Western杂交检测肾脏组织细胞膜IR及IRS-1蛋白表达。结果:苯那普利治疗4周后对糖尿病肾脏肥大有显著抑制作用,对血浆、肾脏组织ACE活性抑制分别达92.00%,88.77%。Western杂交显示糖尿病状态下肾脏组织细胞膜IR及IRS-1蛋白表达比对照组分别高2.1与1.5倍,苯那普利治疗4周可使IR及IRS-1蛋白表达分别低45.74%和47.66%。结论:糖尿病状态下肾脏组织细胞膜IR及IRS-1蛋白表达增加可能与肾脏组织糖代谢异常活跃有关,苯那普利下调IR及IRS-1蛋白表达可能是其对糖尿病肾脏保护作用的重要机制之一。

Effect of benazepril on expression of insulin receptor and its substrate-1 protein in renal tissue cell membrane in diabetic rats

AIM: To study effect of benazepril (an ACE inhibitor) on expression of insulin receptor (IR) and its substrate-1(IRS-1) protein in renal tissue cell membrane in diabetic rats. METHODS: The rats were randomly divided into following groups: control (n=6), streptozotocin induced diabetic (n=7) and diabetic treated with benazepril (n=7). Body weight, kidney weight and kidney weight/body weight were observed after 4 weeks of treatment. ACE activities in plasma, renal tissue were measured by the fluorimetric assay. The expressions of IR and IRS-1 protein were determined by Western blot analysis in renal tissue cell membrane. RESULTS: After 4 weeks of treatment, benazepril significantly ameliorated kidney hypertrophy in diabetic rats. ACE activities in plasma, renal tissue were redunced by approximately 92.00% and 88.77%, respectively. Western blot analysis showed that the expressions of IR and IRS-1 protein were increased by 2.1 and 1.5 folds in renal tissue cell membrane in diabetic rats. However, benazepril reduced expression of IR and IRS-1 protein by 45.74% and 47.66%, respectively. CONCLUSIONS: Increased expression of IR and IRS-1 protein might be related to abnormally active glucose metabolism in diabetic rat kidney. Down-regulation of expression of IR and IRS-1 protein might be one of important machnisms of Benazepril nephroprotection on diabetic rats.