苯那普利对糖尿病大鼠肾组织细胞周期蛋白激酶抑制剂P21^(CIPI)蛋白表达的影响

EFFECT OF BENAZEPRIL ON EXPRESSION OF CYCLIN KINASE INHIBITOR P21 CIP1 PROTEIN IN RENAL TISSUE OF DIABETIC RATS

目的：探讨苯那普利对糖尿病大鼠肾组织细胞周期蛋白激酶抑制剂Ｐ２１ ＣＩＰ１ 蛋白表达的影响。 方法：大鼠随机分单侧肾切除对照组（Ｃ 组） 、糖尿病组（ Ｄ 组） 及糖尿病苯那普利治疗组（ ＤＢ 组） 。１ 周后，应用免疫印迹（ Ｗｅｓｔｅｒｎ 杂交） 分析各组肾皮质Ｐ２１ＣＩＰＩ蛋白表达。血浆、肾皮、髓质血管紧张素转换酶（ＡＣＥ） 活性由荧光分光光度法测得。 结果：单侧肾切除糖尿病大鼠１ 周体重即明显下降（ Ｐ＜ ０－０５） ，肾重／ 体重即肾脏肥大指数却明显增加（ Ｐ＜ ０－０５） ，血浆ＡＣＥ 活性有所下降而肾皮质ＡＣＥ 活性却有所上升。Ｗｅｓｔｅｒｎ 杂交分析表明对照组肾皮质几乎没有Ｐ２１ＣＩＰ１ 蛋白表达，然而，糖尿病肾皮质Ｐ２１ ＣＩＰ１ 蛋白表达明显增加；苯那普利治疗１ 周对肾脏肥大有明显的抑制作用，对血浆、肾皮、髓质ＡＣＥ 活性抑制分别达８９－０ ％ 、７０－０ ％ 、７０－５ ％ ，对肾皮质Ｐ２１ ＣＩＰＩ蛋白表达抑制达６０－０ ％ 。结论：苯那普利对糖尿病肾脏肥大的抑制作用至少部分与Ｐ２１ ＣＩＰＩ蛋白表达降低有关。

To investigate the effect of benazepril on expression of cyclin kinase inhibitor P21 CIP1 protein in renal tissue of diabetic rats. METHODOLOGY Uninephrectomized rats were randomly divided into three groups.Untreated uninephrectomized rats were set as the blank control group(Group C, n =6).Diabetic rats induced by streptozotocin(STZ)were divided into diabetic group(Group D, n =7)and benazepril treated diabetic group(Group DB, n =7)(10mg/kg·day 1 by gavage).Angiotensin converting enzyme(ACE)activities were determined with fluorimetric assay in the plasma,renal cortex and medulla tissue.The expression of P21 CIP1 protein in renal cortex was determined with Western blot analysis. RESULTS At the end of the first week of observation,loss of body weight,increase in renal hypertrophy index (kidney weight/body weight×100),decrease in plasma ACE activity and elevation of renal cortex ACE activity were observed in rats of Group D.The expression of P21 CIP1 protein in renal cortex was hardly detected in rats of Group C,but was significantly enhanced in rats of Group D.Body weight loss and renal hypertrophy index increase were ameliorated in the rats of Group DB.As compared to Group D,ACE activities(in plasma,renal cortex and medulla)were decreased (by 89%,70%,and 70 5%respectively)and expression of P21 CIP1 protein in renal cortex was reduced (by 60%) in rats of Group DB. CONCLUSION Benazepril′s suppression of early diabetic kidney hypertrophy might be associated,at least in part,with a decrease in the expression of P21 CIP1 protein in renal cortex.