金三莪对实验性肝纤维化大鼠TGF-β_1、Smad3、Smad7及CTGF表达的影响

Effect of JinSanE on expression of TGF-β_1,Smad3,Smad7 and CTGF in experimental rats with hepatic fibrosis

[目的]观察中药金三莪抗四氯化碳诱导大鼠肝纤维化的疗效及作用机制。[方法]将50只Wistar大鼠分为正常对照组、模型对照组、中药治疗1组及2组 ,于造模第1周及第4周开始用金三莪治疗。免疫组化技术检测转化生长因子β1(TGF - β1)、Smad3、Smad7及结缔组织生长因子(CTGF)在肝内表达及其在细胞中的定位 ,肝组织电镜检查 ,放射免疫法检测血清透明质酸 (HA)含量。[结果]经中药金三莪治疗后肝纤维化大鼠肝组织内TGF - β1、Smad3及CTGF表达降低 ,而Smad7的表达增加 ,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则主要在肝细胞浆表达。电镜检查中药治疗组大鼠肝细胞结构趋于正常 ,纤维组织变薄。模型组血清HA含量明显高于正常组 (P<0.01) ,中药治疗1、2组血清HA含量明显低于模型组 (P<0.05)。[结论]中药金三莪能有效地减轻四氯化碳诱导肝纤维化大鼠的损伤及纤维化程度 ,其机制可能是抑制肝内TGF - β1。

To investigate the effect and mechanism of JinSanE on liver fibrosis induced by exposure to carbon tetrachloride(CCl4) in rats. Fifty Wistar rats were randomly divided into four groups: healthy controls group,CCl4 model group, Chinese herbs group 1, and group 2. Rats exposed to CCl4 were treated with JinSanE starting at the first and fourth week respectively after CCl4.The expression of transforming growth factor-beta1(TGF-β1), Smad3, Smad7 and connective tissue growth factor (CTGF) in liver tissues and their locations in cells were determined by immunohistochemical method.The liver histopathology was observed by an electron-microscope.The content of serum hyaluronic acid(HA) was determined by radioimmunoassay. The expression of TGF-β1, Smad3 and CTGF was decreased and the expression of Smad7 was increased in liver tissues of rats exposed to CCl4 after the treatment of JinSanE(P<0.05).The TGF-β1, Smad3 and CTGF,as the immuno-positive reaction signals, were mainly expressed in cytoplasm of fiber septum, while Smad7 was mainly in liver cytoplasm.The cell structure in rats treated with Chinese herbs was normal electron-microscopicaly, fibrous tissue was becoming thin.The content of HA was obviously higher in model group than that of healthy group(P<0.01).When compared with the model rats, the content of serum HA was lower obviously in the two groups than that treated with JinSanE(P<0.05).[Conclusion] The Chinese herbs JinSanE has protective effect against the liver injury and can inhibit liver fibrosis induced by CCl4 exposure in rats.The mechanisms may be consisted in its ability of down-regulating TGF-β1, smad3 and CTGF,and up-regulating Smad7 in rats.