The effect of aline Smad7 gene on experimental liver fibrosis in rats

Objective To investigate the effect of aline Smad7 gene on experimental liver fibrosis in rats.MethodsThe experimental liver fibrosis in SD rats was induced by subcutaneous injection of CCl4.Forty male SD rats were randomized to 4 groups.Group 1 was served as normal control group,and the rats in other three groups were given subcutaneous injection of 40% CCl4 at indicated time points.At the end of the second and fourth week,rats in group 2,3,4 were injected with saline,4×109 pfu AdGFP,4×109 pfu AdSmad7 via tail veins,respectively.In the end(CCl4 injection for 15 times),all animals were sacrificed.Standard enzyme method was used to detect the liver function.Meanwhile,the radioimmuno-assay method was used to determine the serum levels of procollagen Ⅲ(PCⅢ),laminin(LN) and collagen IV(CIV).Expression of Smad7 mRNA was evaluated by RT-PCR.At the same time,tissue sections were stained with HE and VG methods and also subjected to immunohistostaining using antibodies against Smad7 and α-SMA.Results Compared with the model group,the serum levels of GPT,PCⅢ and LN in AdSmad7 group decreased conspicuously.RT-PCR indicated the expression of Smad7 mRNA in AdSmad7 group was much higher than that in other three groups.Hepatic pathology was milder in AdSmad7 group amd VG staining demonstrated that liver fibrosis degree in the Smad7 group was obviously milder than that in model group.Liver tissue immunohistostaining showed that there was a high expression of Smad7 in the AdSmad7 group.Meanwhile,the expression of α-SMA decreased significantly.Conclusion Smad7 gene delivery in vivo could improve liver functions,cut down the serum level of PCIII,reduce extracellular matrix deposition, up-regulate the expression of Smad7,down-regulate the expression of SMA, and thereby slow down the process of liver fibrosis.