Effects Of Ginkgo Bibloba Extract On TGF-β₁ And Type Ⅰ Collagen In Hepatic Fibrosis' Rats

AIM: To study the effects of Ginkgo bibloba extract (EGb) on the production of type I collagen and transforming growth factor 1 (TGF-1) in experimental fibrosis rats induced by carbon tetrachloride (CCL4) ,and to investigate the suppressive effects of EGb on liver fibrosis.METHODS: The rat liver fibrosis model was induced by the intraperitoneum injection of CCL4 for 8 weeks. All rats were randomly allocated into four groups: normal control (N) group 12 rats, model (C) group 14 rats, EGb interventional (CE) group 24 rats, only EGb (E) group 12 rats. The EGb interventional group, apart from the administration of CCL4, was treated with EGb 200mg- kg-1 day-1 given orally daily with gavage. At the end of week 4,some of the EGb interventional group rats were sacrificed, and at the end of week 8,all rats were killed. The pathological changes of liver tissue were detected by HE andVG collagen staining; meanwhile, ultra microstructural changes were observed by electron microscope in randomly selected samples. Blood samples were collected for determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (ALB) by enzyme kinetics and tissue malondialdehyde (MDA) were determined by TBA. Immunohistochemistry were assayed for the protein of tissue TGF-betai and collagen type I; at the same time TGF-betal and collagen type I mRNA were evaluated by RT-PCR. RESULTS: The serum ALT, AST and ALB in EGb interventional groups were obviously improved when compared with these of model group(ALT: 171.67 33.63, 113.21 20.45 vs 265 43.27; AST: 313.67 63.44,204.5 30.74 vs 916.5 37.48;ALB: 30.6 2.8,37.2 3.2 vs22.2 1.6, P<0.05 or P<0.01).The content of MDA was significantly different in model and EGb interventional groups(MDA: 3.243 0.31, 2.41 0.5 vs 6.532 0.77, P<0.05 or P<0.01).EGb interventional groups significantly inhibited type I collagen and TGF-1 expression in the liver(TGF-pi/PI0.0126 0.002, 0.0045 0.009 vs0.0383 0.001; CI/PI: 0.0098 0.005 , 0.0041 0.012vs0.0159 0.003 ; P<0.05 or P<0.01); decreased the expression of TGF-1 CI mRNA(TGF-pl: 0.6827 0.285, 0.524 0.009 vs0.9563 0.049; CI : 0.1234 0.034, 0.1075 0.007 vs 0.2361 0.113, P<0.05 or P<0.01).HE and VG stainsshowed that the degree of liver fibrosis in EGb interventional groups was slight than that of model group; electron microscope showed ultrastructure was decreased also. CONCLUSION: EGb could protect hepatocytes,inhibit TGF-β1 and the ECM synthesis,and thereby could prevent the development of liver fibrosis in the experimental animal models.