阻断肾素-血管紧张素系统下调糖尿病大鼠肾组织转化生长因子β受体表达  

Blockade of reninangiotensin system downregulate expression of transforming growth factor receptor in diabetic rats kidney

作　　者：吴永贵[1] 林善锬[1] 

机构地区：[1]上海医科大学附属华山医院肾内科

出　　处：《中华肾脏病杂志》1999年第1期10-13,共4页Chinese Journal of Nephrology

基　　金：美国中华医学基金会基金;国家自然科学基金

摘　　要：目的探讨阻断肾素血管紧张素系统（ＲＡＳ）对糖尿病大鼠肾组织转化生长因子β受体（ＴβＲ）表达的影响。方法大鼠随机分为单侧肾切除组（Ｃ组）、糖尿病组（Ｄ组）和糖尿病苯那普利（１０ｍｇ·ｋｇ－１·ｄ－１，灌胃）治疗组（ＤＢ组）。观察４周后分别用半定量ＲＴＰＣＲ和Ｗｅｓｔｅｒｎ杂交检测各组肾皮质ＴβＲⅠ和ＴβＲⅡｍＲＮＡ和蛋白表达。另外，各组血浆、肾皮质、肾髓质ＡＣＥ活性由荧光分光光度法测得。结果糖尿病组四周即出现明显相对肾重增加和血肌酐水平上升（Ｐ＜００５），尽管血浆ＡＣＥ活性有所下降，肾皮质ＡＣＥ活性却明显增加（Ｐ＜００５）。糖尿病组肾皮质ＴβＲⅠ和ＴβＲⅡｍＲＮＡ和蛋白表达分别比对照组增加１１２、３００倍和１１０、２６２倍；苯那普利治疗四周能明显缓解糖尿病相对肾重增加和血肌酐水平的上升（Ｐ＜００５），对血浆、肾皮质、肾髓质ＡＣＥ活性抑制分别达９２００％、８８７７％、７３４０％（Ｐ＜００１），对肾皮质ＴβＲⅠ和ＴβＲⅡ的ｍＲＮＡ和蛋白表达抑制分别达６３８９％、４４４４％和５２１３％、４７６２％。结论应用苯那普利阻断糖尿病大鼠ＲＡＳ可明显下调肾皮质ＴβＲⅠ和ＴβＲⅡｍＲＮＡ和蛋白?Objective To investigate regulation of renin angiotensin system(RAS) blockade on expression of transforming growth factor receptor(TR) in diabetic rats kidney. Methods The rats were randomly divided by following groups:uninephrectomized(group C)streptozotocin diabetic rats(group D)and diabetic rats treated with benazepril(10 mgkg-1d-1,by gavage,group DB).At 4 week's duration of study,mRNA and protein expressions of TRI and TR were measured by quantitative reverse transcription polymerase chain reaction(RTPCR)and Western blot analysis,respectively.In addition,angiotensin coverting enzyme(ACE)activities were determined by the fluorimetric assay in plasma,renal cortex and renal medulla. Results After 4 weeks,diabetic rats developed increased relative kidney weight and serum creatinine level as well as ACE activities in renal cortex despite a decreased ACE activities in plasma.RTPCR and Western blot analysis demonstrated that mRNA and protein expressions of TRand TR were increased by 112,300 and 110,262 folds in renal cortex,respectively;Administration of benazepril might markedly attenuate elevated relative kidney weight and increased serum creatinine level,ACE activities were reduced by about 9200%,8877% and 7340% in plasma,renal cortex and medulla,respectively,mRNA and protein expressions of TR and TR were diminished by approximately 6389%,4444% and 5213%,4762%,respectively. Conclusion Blockade of RAS with benazepril could significantly downregulate mRNA and protein expressions of TR and TR in diabetic rats kidney.However,its exact mechanism remains to be further determined.

关 键 词：糖尿病 肾脏肥大 苯那普利 TGFΒ RAS 

分 类 号：R587.1[医药卫生—内分泌] R692.02[医药卫生—内科学]