实验性肝纤维化大鼠TGF-β_1、Smad3、Smad7、CTGF的表达及其意义

目的 :研究四氯化碳 ( CCl4 )诱导肝纤维化大鼠肝脏转化生长因子β1( TGF-β1)、Smad3、Smad7和结缔组织生长因子 ( CTGF)的表达及定位。方法 :将 2 4只大鼠随机分为正常对照组与模型组 ,模型组大鼠予以 40 %四氯化碳皮下注射 8周后处死。免疫组化技术检测 TGF-β1、Smad3、Smad7和 CTGF在肝脏的表达及细胞内的定位 ,放射免疫方法检测透明质酸 ,并进行肝组织病理检查。结果 :与正常组大鼠比较 ,模型组大鼠肝内 TGF-β1、Smad3、CTGF表达增加 ,而 Smad7的表达降低。 TGF-β1、Smad3及 CTGF的免疫阳性反应信号主要位于纤维间隔中的细胞浆 ,Smad7主要在肝细胞浆表达 ;模型组大鼠血清 HA及肝组织Van Giseon染色、HE染色和电镜检查均支持肝纤维化改变。结论 :肝内 TGF- β1、Smad3和CTGF表达增强、Smad7表达减弱 ,提示 TGF- β1轴、CTGF参与了肝纤维的发生发展 ,可能作为防治肝纤维化发生发展的新途径之一

Expression and significance of TGF-β1,Smad3,Smad7 and CTGF of liver fibrosis in rats

Objective:To investigate the expression and significance of TGF-β 1,Smad3, Smad7 and CTGF in fibrotic liver induced by the exposure of rats to carbon tetrachloride (CCl 4). Methods: 24 Wistar rats were randomly allocated into two study groups: normal group and CCl 4, model group. The latter group was administered with CCL 4 solution to induce liver fibrosis.Rats were killed after 8 weeks. The expression of transforming growth factor-beta1 (TGF-β 1), Smad3, Smad7 and connective tissue growth factor (CTGF) were detected by an immunohistochemistry in liver tissue. The liver functions of rats were examined ;the serum level of hyalauronic acid (HA) was determined by an RIA; the liver histopathology was also examined by HE,Van Gieson staining and an electron microscopy. Results: Compared with the normal group, the expressions of TGF- β 1, Smad3 and CTGF was increased and the expression of Smad7 was decreased in liver of the model group (P<0.05 or P<0.01). The serum level was significantly increased in liver of the CCl 4 induced rats, the histological changes of fibrosis were also remarkable. Conclusion: TGF-β 1,Smad3,Smad7 and CTGF are involved in the formation and development of liver fibrosis. The axio-TGF β 1 and CTGF play key roles in liver fibrogensis. It may be a new pathway for the treatment of liver fibrosis.