摘要
目的 观察腺病毒介导的反义Smad4基因阻断转化生长因子—β_1(TGF—β_1)信号传导后对肝纤维化的治疗作用。 方法 将腺病毒介导的反义Smad4基因导入四氯化碳/乙醇诱导的大鼠纤维化肝脏,用RT-PCR及western方法观察Smad4的表达,并观察肝脏的病理变化和胶原表达。 结果 纤维化肝脏中Smad4的表达较正常肝脏明显增强,Ⅰ型胶原增多。经转基因处理后大鼠纤维化肝脏中Smad4的表达明显弱于未治疗的纤维化肝脏,Ⅰ型胶原减少;且治疗组肝脏纤维间隔也明显减少,纤维化程度明显减轻。 结论 腺病毒介导的反义Smad4基因能有效阻断TGF—β信号传导系统,减少细胞外基质的产生,从而减轻肝纤维化的程度。
Objective To study the therapeutic effects to block the TGF-β_1(transforming growth factor β_1) signal transduction by antisense Smad4 gene on experimental fibrotic liver. Methods Using the rat model of liver fibrosis induced by Carbon Tetrachloride(CCl_4)/ethanol, we transfected antisense Smad4 gene mediated by adenovirus via portal vein infusion into the liver, and observed the expression of Smad4 by Retro-Polymerase Chain Reaction (RT-PCR) and Western Blot. We also investigated the pathologic features and collagen expression. Results In the non-therapeutic cirrhotic liver, the expression of Smad4 mRNA was significantly increased than normal liver, and so was the collagen Ⅰ. After antisense Smad4 gene being transfccted, the expression of Smad4 mRNA and that of collagen Ⅰ in the therapeutic liver was significantly decreased, compared with the non-therapeutic cirrhotic liver. The fibrous degree of therapeutic liver was also reduced compared with the non-therapeutic fibrous liver. Conclusion These results indicate that because antisense Smad4 gene could block TGF-β_1 signal transduction by reducing the expression of Smad4, so it could inhibit the production of extracellular matrix(ECM) and improve hepatic fibrosis.
出处
《中华肝脏病杂志》
CAS
CSCD
2004年第5期263-266,共4页
Chinese Journal of Hepatology
