血管紧张素Ⅱ受体拮抗剂对肝硬化大鼠TGFβ_1基因表达影响的实验研究

Effects of angiotensin receptor antagonist Losartan on the expression of transforming growth factor (TGF) β_1mRNA in cirrhotic rats

目的 研究血管紧张素Ⅱ (AngiotensinⅡ )Ⅰ型受体 (AT1)拮抗剂Losartan对肝硬化大鼠TGFβ1(transforminggrowthfactorβ1,转化生长因子 β1)基因表达的影响。方法 4 1只雄性SD大鼠分为 4组 :对照组 (10只 )、模型组 (11只 )、及Losartan治疗组 (2 0只 )〔早期 (10 )、中期 (10 )〕 ,除对照组外所有大鼠均给予 5 0 %CCL4灌胃 ,3mg·kg-1·5d-1,共 9周。治疗组 :早期组同时给予血管紧张素受体拮抗剂Losartan灌胃 ,中期组于造模中期 (5周 )开始给药 ,用量 10mg·kg-1·d-1至处死前。实验结束后 ,处死取肝脏液氮冻存及福尔马林固定标本 ,分别行免疫组织化学及RT PCR检测 ,TGFβ1蛋白及基因表达情况。结果 与正常组相比 ,模型组TGFβ1表达明显增强 ,由 0 93± 0 0 5升高到 1 94± 0 13(P <0 0 1) ,而两治疗组与模型组相比 ,losartan明显降低了TGFβ1mRNA的表达 ,分别降至 1 17±0 16、1 0 2± 0 11(P <0 0 5 ) ,而早、中期两组差异无显著意义 (P >0 0 5 )。

Objective To investigate effects of angiotensin Ⅱ receptor antagonist Losartan on the expression of TGF β 1mRNA in rats with cirrhosis and the mechanism.Method Forty one male SD rats were divided into normal control ( n =10), cirrhotic control ( n =11), and Losartan treated cirrhotics ( n =20) with Losartan (10?mg·kg -1 ·d -1 ) treatment started on the first day along with CCl 4 administration and on the 5th week, respectively.Expression of TGF β 1 mRNA was examined with reverse transcriptase polymerase chain reaction (RT PCR).The expression of TGF β 1 protein was assayed with immunochemistry.Result Expression of TGF β 1 mRNA and TGF β 1 protein were up regulated in rats with cirrhosis (from 0 93±0 05 to 1 94±0 13, compared with the normal rats P <0 01).Compared with the untreated cirrhotic rats Losartan treatment significantly reduced mRNA and protein levels of TGF β 1 (1 17±0 16 and 1 02±0 11 respectively,all P <0 05).Conclusion Losartan significantly decreases the expression of TGF β 1 in cirrhotic rats.