培哚普利和缬沙坦对肝纤维化大鼠TGF-β_1及其Ⅱ型受体mRNA与Smad3、Smad7表达的影响  

Effects of perindopril and valsartan on expression of TGF-β_1 and TGF-β receptor Ⅱ mRNA,Smad3 and Smad7 in experimental hepatic fibrosis in rats

作　　者：龚作炯[1] 宋仕玲[1] 黄砚青[1] 阮鹏[1] 张志荣[1] 

机构地区：[1]武汉大学病毒学教育部重点实验室武汉大学人民医院感染科,430060

出　　处：《江苏医药》2004年第6期403-405,i001,共4页Jiangsu Medical Journal

摘　　要：目的　观察培哚普利和缬沙坦抗大鼠肝纤维化的疗效。方法　 6 0只Wistar大鼠随机平均分为 4组 :正常组、模型组、培哚普利治疗组和缬沙坦治疗组。四氯化碳诱导大鼠肝纤维化模型 ,治疗组于造模第 4周开始分别予以培哚普利和缬沙坦灌胃。RT PCR检测肝组织转化生长因子 β1(TGF β1)、Ⅱ型受体 (TGFRⅡmRNA) ;免疫组化技术检测TGF β1、Smad3及Smad7在肝内的表达及定位 ,肝组织HE染色检测病理改变。结果　与模型组大鼠比较 ,经培哚普利或缬沙坦治疗大鼠肝内TGF β1与TGFRⅡmRNA、以及Smad3蛋白表达明显降低 ;而Smad7的表达增加。TGF β1与Smad3的免疫阳性反应信号主要位于纤维间隔中的细胞浆 ,Smad7则主要在肝细胞浆表达 ,上述物质在两种药物组之间表达差异无显著性 (P >0 0 5 )。培哚普利或缬沙坦治疗后肝小叶均趋于正常 ,纤维间隔明显变薄。结论　培哚普利或缬沙坦均能有效地减轻肝纤维化大鼠的肝脏损伤及纤维化程度 ,其机理可能与直接或间接抑制肝内TGF β1、与TGFRⅡmRNA及Smad3表达 ,并促进Smad7表达有关。Objective To investigate the effect and mechanism of the perindopril,an angiotensin-converting enzyme inhibitor,and valsartan,an angiotensin Ⅱ receptor blocker on TGF-β 1 and TGF-β receptor Ⅱ mRNA,Smad3 and Smad7 in fibrotic hepatic livers in rats.Methods 60 Wistar rats were randomly divided into four study groups(each group,n=15):healthy controls,hepatic fibrosis models,rats treated with perindopril and valsartan,starting at the fourth week since the rats exposed to CCl 4.All rats were sacrificed their blood and liver were collected for further determinations at the eighth week.The effects of perindopril and valsartan were evaluated of the level of transforming growth factor-betal (TGF-β 1),and TGF receptor (TGFR Ⅱ)mRNA in liver tissue by RT-PCR,the expressions and sites of TGF-β 1,Smad3 and Smad7 in liver tissue by immunohistochemical staining.The liver histopathology was also examined by HE staining,and the liver function and serum hyaluronic acid(HA) were examined by biochemsitry and RIA respectively.Results Compared with the health controls,the levels of TGF-β 1,TGFRⅡ mRNA and the expression of Smad3 were significantly decreased in the two treated groups,and the expression of Smad7 was also remarkably increased in liver of rats treated with perindopril or valsartan (P<0.05 or P<0.01).The histological changes of fibrosis,liver function and HA were also obviously improved in treated rats.Conclusion Perindopril or valsartan has protective effect on liver injury and can inhibit hepatic fibrosis induced by CCl 4 in rats.Their mechanisms may be associated with their effects of down-regulating TGF-β 1,TGFRⅡ mRNA and Smad3,up-regulating Smad7 and result in suppressing the activation of hepatic stellate cells.

关 键 词：培哚普利 缬沙坦 肝纤维化 大鼠 TGF-β1 Ⅱ型受体mRNA SMAD3 SMAD7 受体阻滞剂 转化生长因子-β1 

分 类 号：R575.2[医药卫生—消化系统]