反义Smad4对大鼠纤维化肝脏金属蛋白酶及其抑制剂的调节

Regulated expression of the MMPs and TIMPs in rat liver fibrosis by antisense Smad4 gene

目的 探讨反义Smad4基因对纤维化肝金属蛋白酶及其抑制剂表达的调节作用。方法 通过门静脉灌注将高滴度的反义Smad4的重组腺病毒载体导入大鼠纤维化肝脏。结果 RT PCR证实肝脏内有反义Smad4的转录和表达。同时采用免疫组化检测发现 ,转基因组肝脏内源性Smad4表达降低 ,TIMP1、TIMP2的表达减少 ,MMP2和MMP9的表达下调。结论 反义Smad4能调节纤维化肝脏内源性TIMPs和MMPs的表达 。

Objective To investigate the role of antisense Smad4 cDNA in regulation the expression of MMPs and TIMPs in rat liver fibrosis.Method A high titer,recombinant adenoviral vector carried antisense cDNA for Smad4 (AdATSmad4) produced by 293 packaging cells was introduced into rat fibrotic liver via portal vein infusion.Results RT PCR demonstrated that the antisense Smad4 cDNA was transcripted and expressed.At the same time,immunohistochemistry showed that the expression of endogenous Smad4 protein was sgnificantly decreased in the transfected rat fibrotic liver.Moreover,antisense Smad4 RNA suppressed the expression of TIMP1,TIMP2,and dow regulated the expression of MMP2 and MMP9.Conclusion We conclude that antisense Smad4 can regulate the expression of MMPs or TIMPs in liver fibrosis rat,and could become a potent antifibrogenic tool in chronic liver disease.