Effect Of Chymase Inhibitors On Expression Of TGF-β1,TβRⅠ And TβRⅡ In Liver Tissue Of Rats With Hepatic Fibrosis

Objective:Chymase inhibitors(Chymase inhibitors,Chy-I)on liver fibrosis model of rat hepatic fibrosis pathological change and hepatic fibrosis of Transforming growth factorβ 1(Transforming growth factor β1,TGF-β1)and Transforming growth factor βI receptor(Transforming growth factor β receptor-I,TβRⅠ),Transforming growth factorβII receptor(Transforming growth factor β receptor-II,TβRⅡ)expression and the influence of the regulation mechanism.Method:Thirty-two male Wistar rats were selected.Models were prepared and divided into normal group,model group and Chy-I group.Model group and Chy-I group were used to make hepatic fibrosis tissue model of rats with carbon tetrachloride(CCl4).The Chy-I group was intragastric administrated with Chy-I at a dose of 10mg/kg per day while establishing the model.Weekend 8 of experimental will kill animals.Hepatic fibrosis samples were exsamined by HE staining,and immunohistochemical stining.and then by fluorescence quantitative polymerase chain reaction(q PCR)detection of TGF-β1,TβRⅠ and TβRⅡ gene expression;Western blot method between groups in the liver tissue of TGF-β1,TβRⅠ and TβRⅡ protein expression levels.Results:1.Compared with model group,the hepatic pathological changes were significantly improved in the group of the chymase inhibitor treatment.2.The quantity of TGF-β1,TβRⅠ and TβRⅡ-immunoreactive cells were reduced in the Chy-I group than that in model group.3.Fluorescence quantitative polymerase chain reaction(q PCR)detection in the rat hepatic fibrosis TGF-β1 and TβRⅠ,TβRⅡ gene expression shows: compared with normal group,model group TGF-β 1 and TβRⅠ,TβRⅡ m RNA expression were significantly increased(P<0.05).Compared with model group,the treatment group TGF-β1 and TβRⅠ、TβRⅡ m RNA expression decreased(P < 0.05).4.Western blot analysis of TGF-β1,TβRⅠ and TβRⅡ protein expression in hepatic fibrosis of each group showed that compared with the normal group,the expression of TGF-β1,TβRⅠ and TβRⅡ protein in model group were significantly increased(P< 0.05).Compared with model group,the protein expressions of TGF-β1,TβRⅠ and TβRⅡ in Chy-I group were decreased(P < 0.05).Conclusion:1.Compared with model group,the hepatic pathological changes were significantly improved in the group of the chymase inhibitor treatment.2.TGF-β1 is the most powerful promoter in the process of hepatic fibrosis,which may play a role by acting on two receptors,TβR I and TβR II.