苯那普利对糖尿病大鼠肾皮质p21^(CIP1)蛋白表达的调节及其机制  

Regulation of renal cortex p21 CIP1 protein expression by benazepril and its mechanism in diabetic rats

作　　者：林善锬[1] 吴永贵[1] 余毅 周江华[1] 

机构地区：[1]上海医科大学华山医院肾内科,200040

出　　处：《中华内分泌代谢杂志》1999年第4期220-224,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：美国中华医学基金;国家自然科学基金

摘　　要：目的　研究苯那普利对糖尿病大鼠肾皮质ｐ２１ Ｃ Ｉ Ｐ１ 蛋白表达 的调节及其机制。方法大鼠随机分单侧肾切除对照组、糖尿病组及糖尿病苯那普利（１０ ｍ ｇ·ｋｇ － １ ·日－ １ ，灌胃） 治疗组。应用 Ｎｏｒｔｈｅｒｎ 杂交检测各组肾皮质转化生长因子β１（ Ｔ Ｇ Ｆβ１） ｍ Ｒ Ｎ Ａ 表达， Ｗｅｓｔｅｒｎ 杂交检测各组肾皮质 Ｔ Ｇ Ｆβ１ 及ｐ２１ Ｃ Ｉ Ｐ１ 蛋白的表达。另外，血浆、肾皮、髓质血管紧张素转换酶（ Ａ Ｃ Ｅ） 活性由荧光分光光度法测定。结果　糖尿病大鼠一周后体重即明显下降（ Ｐ＜ ０ ．０５） ，伴肾重／ 体重明显增加（ Ｐ＜ ０ ．０５） ，血浆 Ａ Ｃ Ｅ 活性有所下降而肾皮质 Ａ Ｃ Ｅ 活性则有所上升。 Ｎｏｒｔｈｅｒｎ 杂交表明糖尿病组肾皮质 Ｔ Ｇ Ｆβ１ｍ Ｒ Ｎ Ａ 表达约比对照组上升６３ ．６ ％ 。肾皮质 Ｔ Ｇ Ｆβ１ 及 Ｐ２１ Ｃ Ｉ Ｐ１ 蛋白表达也明显增加；苯那普利治疗一周对肾脏肥大有明显的抑制作用，对血浆、肾皮、髓质 Ａ Ｃ Ｅ 活性抑制分别达８９ ．０ ％ 、７０ ．０ ％ 、７０ ．５ ％ ，对肾皮质 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 及 Ｔ Ｇ Ｆβ１ 和ｐ２１ Ｃ Ｉ Ｐ１ 蛋白表达抑制分别达４７ ．７ ％ ，４９ ．５ ％ ，６０ ?Objective To investigate the regulation of renal cortex p21 CIP1 protein expression by benazapril and its mechanism in diabetic rats. Methods The rats were randomly divided into following groups: uninephrectomized rats, streptozotocin induced diabetic rats and diabetic rats treated with benazepril (10mg·kg -1 ·d -1 , by gavage). Angiotensin converting enzyme (ACE) activities were determined by fluorimetric assay in plasma and renal cortex and medulla. Renal cortex transforming growth factor β1 (TGFβ1) mRNA expression was assessed by Northern blot analysis, and TGFβ1 and p21 CIP1 protein expression was measured by Western blot analysis. Results After 1 week, diabetic rats developed a body weight loss, an increased kidney weight/body weight and an elevated ACE activity in renal cortex despite a decreased ACE activity in plasma. Northernblotanalysisshowedthatrenal cortex TGFβ1 mRNAexpressionindiabeticrats increased by 63.6%, as against uninephrectomized rats. Western blot analysis noted that TGFβ1 and p21 CIP1 protein expression was also increased. Administration of benazepril for one week could significantly suppress kidney hypertrophy and ACE activities were reduced by 89.0%, 70.0% and 70.5% in plasma and renal cortex and medulla, respectively. Expressions of TGFβ1 mRNA, TGFβ1 and p21 CIP1 protein were decreased by 47.7%, 49.5% and 60.0%, respectively. Conclusion Benazepril may suppress increased p21 CIP1 protein expression in diabetic rats and its mechanism may partially be related to down regulation of TGFβ1 expression.

关 键 词：苯那普利 糖尿病肾病 p21^CIP1蛋白 TGFΒ1 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]