Effects Of Hepatocyte Growth Factor On Liver Fibrosis In Rats And Its Possible Mechanism

Objective: To investigate the effect of HGF (hepatocyte growth factor) on expression of MMP-13 (matrix metalloproteinase-13) , TIMP-1 (tissue inhibitors of metalloproteinase -1) and TGFβ-1 (transforming growth factorβ-1) in experimental hepatic fibrosis in rats and its possible mechanism.Methods: Wister Rats were randomly divided into three groups: normal control group, model group and HGF group. The latter two groups were administered with CCl4 and salad oil solution to induce hepatic fibrosis. HGF group was treated with HGF at the 3th week after CCl4 and salad oil solution administration. All animals were sacrificed at the end of the 8th week. Blood and hepatic tissue specimens were taken. Histological grade was analysed by HE and VG stain. Biochemical, radioimmunological examinations were used to determine the level change of ALT,AST,HA,Ⅳ-c in serum. Immunohistochemical assay was used to determineα-SMA, MMP-13,TIMP-1 and TGFβ-1 expression in liver tissue.Results:1. Specimens from model control group showed apparent formation of fibotic septa, encompassing regenerated hepatocytes into pseude-lobules. However less necrotic inflammation and fibrogenesis were found in HGF treated group by HE and VG staining(P<0.05).2. Compared with model group, serum ALT,AST,HA,CⅣlevel were markedly dropped in HGF treated group (P<0.05,respectively).3. Hepatic tissue expression ofα-SMA,TIMP-1 and TGFβ-1 were significantly decreased, while MMP-13 expression was increased in HGF treated group Compared with model group (P <0.05).Conclusion:HGF could inhibit hepatic fibrogenesis derived from chronic liver injury, retard the development of cirrhosis. Its possible mechanism involves upregulating MMP-13 exprssion, inhibiting TGFβ-1 expression , and thereby, decreasing TIMP-1 activity, preventing HSC activation and improving the balance of synthesis and degradation of extracellular matrix.