中药软肝饮对CCl_4诱导的肝纤维化大鼠TGF-1/Smad信号通路的影响

Effects of Traditional Chinese Medicine Ruanganyin on TGF-1/Smad Signaling Pathway in Carbon Tetrachloride-induced Hepatic Fibrosis of Rats

[目的]研究中药软肝饮对CCl4诱导的大鼠肝纤维化肝脏TGF-1及Smad3,Smad7表达的影响,探讨其抗纤维化的作用机制。[方法]Wistar大鼠40只,随机分成正常对照组,模型对照组,软肝饮治疗组,鳖甲软肝片对照组,采用CCl4背部皮下注射构建肝纤维化模型,行HE和VG染色,光镜下观察肝组织肝纤维化程度。同时免疫组化SABC方法检测各组TGF-1、Smad3和Smad7的表达。[结果]与正常对照组相比,模型组TGF-1、Smad3表达明显增强,Smad7表达明显下降。经软肝饮治疗后大鼠肝脏TGF-1表达比模型组减弱。软肝饮同时下调Smad3的表达,上调Smad7的表达。另外,软肝饮组大鼠肝脏病理变化显著改善。[结论]肝炎平对大鼠肝纤维化肝脏TGF-1/Smad信号通路有明显的影响,能抑制CCl4诱导的大鼠肝纤维化,其作用机制可能为抑制TGF-1表达,下调Smad3及上调Smad7的表达。

[Aim] To study the effects of Ruanganyin on TGF-1,Smad3,Smad7 expressions of the experimental hepatic fibrosis induced by carbon tetrachloride （CCl4） in rats,and to explore its anti-fibrotic molecular mechanism. [Method] Forty healthy Wistar rats were randomly divided into normal control group, vacant control group, CCl4-induced hepatic fibrosis group, and Ruanganyin treated group. The rats in normal group were treated with normal saline by intragastrical irrigation, and the other groups were subcutaneous injected with CCl4 to establish hepatic fibrosis model. The histological changes of the liver tissues were examined by pathological examination. The protein expression of transforming growth factor beta 1 （TGF-1） and Smad3, Smad7 were measured by immunohistochemical technique. [Result] In comparison with those inmodel group, the levels of TGF-1 were significantly decreased after treatment with Ruanganyin. Meanwhile, the levels of Smad3 was also down-regulated. However, the level of Smad7 expression was significantly up-regulated. The pathological changes of liver tissues in Ruanganyin groups were also markedly alleviated. [Conclusion] Ruanganyin has significant inhibitory effects on CCl4-induced hepatic fibrosis in rats,and its mechanism may be associated with the inhibition of TGF-1 expression,down-regulation of Smad3 expression and up-regulation of Smad7 expression.