转化生长因子β_1在肾小球硬化大鼠的表达及苯那普利和芦沙坦的治疗作用  

Expression of Transforming Growth Factor-β_1 in Rat Glomerulosclerosis and the Effects of Benazepril and Losartan

作　　者：纪泽泉[1] 黄翠雯[1] 陈波[2] 林明辉[1] 梁成结[3] 陈盛强[2] 孙卫文[2] 

机构地区：[1]广州医学院第二附属医院儿科,广州510260 [2]广州医学院第二附属医院实验动物研究中心,广州510260 [3]广州医学院第二附属医院分子生物学实验中心,广州510260

出　　处：《中国中西医结合肾病杂志》2004年第8期443-446,共4页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：广州市科委重点科技攻关项目 (No .1999-K -0 0 7-0 2 )

摘　　要：目的 :探讨肾小球硬化大鼠肾组织转化生长因子 β1(TGF - β1)基因及蛋白表达 ,以及苯那普利和芦沙坦的影响及其意义。方法 :大鼠随机分成假手术组 (C组 ) ,肾小球硬化组 (D组 ) ,肾小球硬化苯那普利治疗组 (DB组 )和肾小球硬化芦沙坦治疗组 (DL组 ) ,治疗 6周后用RT -PCR检测肾皮质转化生长因子 β1(TGF - β1)mRNA和Ⅳ型胶原 (ColⅣ )mRNA表达 ,WesternBlotting检测TGF - β1蛋白表达 ,免疫组化测定肾组织ColⅣ ,并观察病理及生化改变。结果 :肾小球硬化组出现明显蛋白尿 ,血白蛋白下降及胆固醇上升 ,与假手术组比较有统计学差异 (P <0 .0 5或P <0 .0 1) ,肾小球系膜细胞增生 ,细胞外基质沉积 ,肾皮质TGF - β1mRNA和蛋白表达分别比假手术组增加 3.5 9倍和 2 .6 0倍 ,ColⅣmRNA和蛋白表达分别比假手术组升高 2 .5 7倍和 1.4 0倍。苯那普利和芦沙坦分别治疗 6周后 ,能明显减轻肾病生化改变及病理改变 ,肾皮质TGF - β1mRNA和蛋白表达分别下调 4 6 %、5 3%和 5 5 %、5 9% ,ColⅣmRNA和蛋白表达分别下降 4 6 %、5 4 %和 4 3%、4 8%。结论 :苯那普利和芦沙坦通过下调TGF - β1mRNA和蛋白的表达 ,减少肾小球细胞外基质的沉积 ,延缓肾小球硬化。Objective:To investigate changes of the mRNA and protein expressions of transforming growth factor-β1(TGFβ1) in rat glomerulosclerosis and the effects of Benazepril and Losartan.Methods:Rats were randomly divided into four groups: sham-operation control(group c), glomerulosclerosis rats(group D), glomerulosclerosis rats treated with Benazepril(group DB) or with Losartan(group DL). After 6 weeks of Benazepril or Losartan treatment, the mRNA expressions of TGF-β 1 and Collagen Ⅳ were measured by reverse transcription polymerase chain reaction(RT-PCR). The protein level of TGF-β 1 was detected by western blot analysis, and the expression of Collagen Ⅳ was analyzed by immunohistochemistry.Results:Group D presented with massive proteinuria, hypoalbuminemia and hypercholesterolemia, which had significant difference with group C(P<0.05or<0.01). BUN and creatinine were elevated. RT-PCR and Western blot analysis demonstrated that the cortical mRNA and protein expressions of TGF-β1 increased by 3.59 and 2.60 folds.The mRNA and protein expressions of Collagen increased by 2.57 and 1.40 folds.After 6 weeks of the treatment with Benazepril or Losartan, the deposition of extracellular matrix in two treatment groups was significantly lower than that in glomerulosclerosis group. The mRNA and protein expressions of TGF-β 1 were reduced by 46%, 53% and 55%, 59%. The mRNA and protein expressions of Collagen Ⅳ were reduced by 46%, 54% and 43%, 48%, respectively.Conclusion:Benazepril and Losartan reduces the deposition of extracellular matrix by down-regulating the mRNA and protein expressions of TGF-β1 in rat glomerulosclerosis.

关 键 词：转化生长因子Β1 肾小球硬化 大鼠 表达 苯那普利 芦沙坦 治疗作用 

分 类 号：R692.6[医药卫生—泌尿科学]