血管紧张素转换酶抑制剂对肝纤维化大鼠TGFβ,TGFR Ⅱ,Smad3,7表达的影响  

Effects of angiotensin-converting enzyme inhibitor on expression of TGFβ_1 and TGFR Ⅱ mRNA, Smad3 and Smad7 on CCI_4-inducing rat hepatic fibrogenesis

作　　者：龚作炯[1] 宋仕玲[1] 阮鹏[1] 向龙奎[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

出　　处：《世界华人消化杂志》2004年第5期1132-1135,共4页World Chinese Journal of Digestology

摘　　要：目的:观察血管紧张素转换酶抑制剂培哚普利抗大鼠肝纤维化的疗效及作用机制. 方法:将80只Wistar大鼠随机分为5组,每组16只大鼠. A组为正常对照组;B,C组为肝纤维化模型组;D,E组为培哚普利治疗组.B,C,D和E组大鼠均给四氯化碳8 wk诱导肝纤维化;D,E组大鼠分别于4,8 wk予以培哚普利灌胃治疗.A,B,D组大鼠于8 wk处死,C,E 组大鼠于12 wk处死.RT-PCR检测大鼠肝组织TGFβ1与TGFRⅡmRNA;免疫组化技术检测Smad3及Smad7在肝内的表达及定位;HE染色及电镜检测检测肝组织病理改变. 结果:与模型组大鼠比较,RT-PCR显示经培哚普利治疗大鼠肝内TGFβ1与TGFRⅡmRNA(P<0.05或P<0.01), 以及Smad3表达明显降低;而Smad7的表达增加,Smad3 的免疫阳性反应信号主要位于纤维间隔中的细胞质, Smad7则主要在肝细胞质表达.大鼠肝组织TGFβ1与TGFR ⅡmRNA,Smad3与Smad7在D组与E组表达比较差异有显著性(P<0.05),而上述物质在B组与C组比较差异无显著性(P>0.05).培哚普利治疗后,大鼠肝小叶结构趋于正常, 纤维间隔明显变薄,肝细胞超微结构改善. 结论:培哚普利能有效地减轻肝纤维化大鼠的肝脏损伤及纤维化程度.其机制可能与抑制肝内TGFβ1与TGFRⅡmRNA 及Smad3表达,促进Smad7表达有关.AIM: To assess the effects of an angiotensin-converting enzyme inhibitor, perindopril on preventing hepatic fibrosis induced by CCl4 in rats and to investigate the alternation of the expression of transforming growth factor-beta1 (TGFβ1) and its receptor Ⅱ (TGFR Ⅱ) and smads on liver tissues. METHODS: 80 Wistar rats were randomly allocated into five groups: group A was healthy controls, groups B and C were hepatic fibrotic models induced by carbon tetrachlo-ride (CCl4), groups D and E were models treated with perindopril starting at the first and fourth week since rat exposured CCl4. Except for group A, rats were subcutane-ously injected with CCl4for eight weeks. Rats in groups A, B and D were killed at eighth week, and rats in groups C and E were sacrificed at twelveth week. The blood and liver of rats were collected for further determinations. The effects of perindopril on hepatic fibrosis were evaluated by detecting the level of TGFβ1 and TGFR Ⅱ mRIMA by RT-PCR. And the expression and its localization of Smad3 and Smad7 in liver tissue by an immunohistochemical staining. The liver histopathology was also examined by HE staining and an electron microscope. RESULTS: Contrasted to the groups B and C, the level of TGFβ1, TGFR Ⅱ mRNA and the expression of Smad3 were significantly decreased in groups D and E, and the expression of Smad7 was also significantly increased in liver of the two groups (P<0.05 or P<0.01). The expression of TGFβ1 and TGFR Ⅱ mRNA, Smad3 and Smad7 were not different between groups B and C (P>0.05), but there was a significant difference between groups D and E (P<0.05). Compared with model groups, the histological changes of fibrosis and the dynamic ultrastructureal alterations in rats treated with perindopril were also obviously improved (P<0.05). CONCLUSION: The angiotensin-converting enzyme inhibitor, perindopril has a protective effect on liver injury and can ameliorate hepatic fibrosis in rats induced by CCl4. The mechanisms of perindopril anti-fibrosis may be associated wit

关 键 词：血管紧张素转换酶抑制剂 肝纤维化 大鼠 TGFΒ TGFRⅡ SMAD3 SMAD7 免疫组化 

分 类 号：R575.2[医药卫生—消化系统]