Effects of traditional Chinese medicine prescription Dan-shao-huaxian capsule on expression of Smads in rat liver of hepatic fibrosis

AIM: To investigate the effect of Dan-shao-hua-xian( DSHX) capsule,a Chinese medicine prescription,on the expression of Smad2 /3,Smad4 and Smad7,downstream signal proteins of TGF-β,in carbon tetrachloride( CCl4)-induced rat hepatic fibrosis,and to evaluate the application of Smads as potential targets for anti-fibrosis. METHODS: Forty-eight Wistar rats were randomly divided into three groups: normal control group,CCl4-induced hepatic fibrosis group and DSHX treatment group. The rats in both CCl4-induced hepatic fibrosis group and DSHX treatment group were induced by subcutaneous injection of CCl4,drinking alcohol,giving diet of hyperliprosis and hypoprotein for 8 weeks to establish the hepasis fibrosis model. The hepatic fibrosis rats in DSHX treatment group were treated with DSHX capsule ( 1 g/kg,po) once per day for 8 weeks. Finally,the liver index,serum hyaluronic acid ( HA) ,alanine aminotransferase ( ALT) ,the degree of hepatic fibrosis and the urinary excretion of hydroxyproline ( Hyp) were evaluated. Meanwhile,the techniques of immunohistochemistry,Western blotting and qRT-PCR were applied to detect the expression of Smad2 /3 and Smad4 and Smad7 at both mRNA and protein levels. RESULTS: Compared to hepatic fibrosis group, the liver index,serum levels of HA and ALT,and the degree of hepatic fibrosis were all significantly reduced,and the urinary excretion of Hyp was increased in DSHX treatment group. The mRNA and protein expression of Smad7 in the liver tissues in DSHX treatment group significantly increased as compared to that in hepatic fibrosis group. However,the protein expression of Smad2 /3 and Smad4 decreased and the mRNA expression of Smad2 /3 and Smad4 was unchanged as compared to that in hepatic fibrosis group. CONCLUSION: Dan-shao-hua-xian capsule promotes the transcription and expression of Smad7 to exert its feedback suppression on TGF-β/Smad-induced hepatic fibrosis signal transduction pathway. This might be one of the mechanisms by which Dan-shao-hua-xian capsule inhibits the process of hepatic fibrosis,and Smad7 might be the potential target.