【摘要】 目的探讨反义Smad4基因阻断TGF β信号传导系统对抗小鼠肝脏纤维化的效果。方法将反义Smad4基因导入CCl4 /乙醇诱导的昆明小鼠纤维化肝脏 ,用Southernblot检测整合情况 ,用Northernblot、RT PCR及Westernblot方法观察Smad4的表达 ,比较各组小鼠肝脏纤维化程度。结果反义Smad4基因可整合到病毒处理组小鼠肝脏。纤维化肝脏Smad4表达较正常组明显增强。经转基因处理后 ,小鼠纤维化肝脏Smad4的表达明显弱于对照组 ,肝脏纤维间隔不同程度地减少、变窄或不完整 ,纤维化程度也有所减轻。结论反义Smad4基因能有效减少Smad4基因的表达 ,进而部分阻断TGF β信号传导系统 ,以阻止贮脂细胞的活化 ,减少细胞外基质的产生 ,从而减缓肝纤维化的发展。更多还原

【Abstract】 ObjectiveTo study the effect of TGF-β 1 signal transduction blocked by antisense-Smad 4 gene on progression of experimental liver fibrosis of Kunming mice.MethodsWe transfered retrovirus-mediated antisense Smad 4cDNA into the CCl4/ethanol induced cirrhotic liver of Kunming mouse model to investigate the antisense-Smad 4 gene integration by Southern blot. The expression of Smad 4 in cirrhotic liver was observed by Northern blot, RT-PCR, and Western blot. The fibrotic degree of the livers among the three groups were compared.ResultsThe antisense-Smad 4 gene was confirmed to integrate into the liver of the retrovirus-treated mouse .In the non-treated cirrhotic liver, the expression of Smad 4 mRNA was significantly increased than normal liver, the antisense Smad 4 gene could decrease the expression of Smad 4. Compared with the non-treated liver, the fibrotic septa of the liver in the retrovirus-treated mouse were fewer,narrow, and incomplete,and their fibrotic degree of the treated-liver was reduced.ConclusionThese results indicate that antisense-Smad 4 gene can reduce the expression of Smad 4,inhibit the progression of liver fibrosis.更多还原