Effects Of Extract Of Ginkgo Biloba On Liver Fibrosis And Its Mechanisms

Hepatic fibrosis represents the response of the liver to diverse chronic insults such as parasitic disease, chronic viral infection (hepatitis B and C), immunologic attack (autoimmune hepatitis), hereditary metal overload, toxic damage, etc. Because of the worldwide prevalence of these insults, liver fibrosis is common and is associated with significant morbidity and mortality. It is predominantly characterized by excessive accumulation of extracellular matrix (ECM) components in the liver, caused by an imbalance between the synthesis, degradation and deposition of ECM. Up to now, no effective treatment of hepatic fibrosis is available for clinical use, in particular, no method for enhancing degradation and resolution of these deposited ECM, and reversing hepatic fibrosis. Extract of Ginkgo biloba (EGB) is an extract from green leaves of the Ginkgo biloba tree. EGB has been shown to have a SOD-like activity and hydroxyl radical scavening activity. The role of EGB in prevention and treating CCl4-induced hepatic fibrosis were established in order to provide theoretical and experimental basis for clinic.The study was divided into two parts: preventive experiment and therapeutic experiment. CCl4 was injected intraperitoneally using 0.15ml per rat (diluted 1:1 in liquid paraffin) twice weekly for 8 weeks to produce liver fibrosis. 200 mg kg-1 day-1 EGB was given orally daily with gavage to prevent or treat liver fibrosis. In preventive experiment, the rats were divided into four groups: normal group (N group, paraffin+saline), EGB group (E group, paraffin+EGB), CCl4 group (C group, CCl4+saline) and CCl4+EGB group (CE group, CCl4+EGB). CCl4 and EGB or saline were given at the same time for 8 weeks. All animals were killed at the end of the eighth week. In therapeutic experiment, the rats were divided into three groups: Z group, Y group and Z group. After confirmation of liver fibrosis, EGB or saline wasgiven for 2 weeks to Y group and Z group. The preventive and therapeutic effects of EGB in pathologic and functional changes were comparatively assayed.The model of CCl4-induced liver fibrosis was established in rats. The levels of serum ALT (alanine aminotransferase), AST (aspartate aminotransferase), Tbil (total bilirubin), Alb (albumin) and total protein (TP) were examined with auto-motion biochemical analyzor. And the level of liver tissue MDA were determined also. The histological changes were observed by light microscope. Histological studies (H&E, Gorden-Sweet and Masson staining) were examined. The expressions of aSMA in hepatic tissue was detected by immunohistochemistry. The expression of MMP-13, -2, TIMP-1 and TIMP-2 mRNA were detected by RT-PCR.The parameters of liver function and the degree of hepatic fibrosis deteriorated in C group compared with N group (liver fibrosis: u=6.18, P<0.01; collagen: t=25.11; reticulum: t=27.14, MDA: t-=9.64, aSMA: t=4.94, ALT: t=6.82, AST: t=7.14, Tbil: t=6.06, Alb: t=12.21, TP: t=13.79, P<0.001), which indicated injury of liver of C group. The liver function and the degree of hepatic fibrosis in CE groups improved compared with those in C group (ALT: t=3.89, AST: t=5.06, Tbil:t=4.22, TP: t=11.01, Alb: t=7.04, collagen, t=9.85, reticulum: t=18.94, aSMA: t=6.67, P<0.001; liver fibrosis: u=3.55, P<0.01; MDA: t=3.71, P<0.005), which indicated EGB could prevent and improve liver injury and hepatic fibrosis. They were lower in CE group compared with C group, but still higher than that in N group(ALT: t=3.27, aSMA: t=3.02, P<0.005; AST: t=2.04, Tbil: t=2.50, Alb: t=2.59, P<0.05; TP: t=4.04, collagen: t=16.79, P<0.001; liver fibrosis: u=3.95, P<0.01; MDA: t=6.67, P<0.001; reticulum: t=1.71, P>.05) . It was suggested that EGB had preventive effect of hepatic fibrosis but not completely. The relative expression of MMP-2 and TIMP-1, -2 mRNA in liver tissue of C group increased compared with N group (MMP-2: t=29.37, TIMP-1: t=27.56, TIMP-2: t=25.08, P<0.001) , but decreased in CE group compared with C group (MMP-2: t=14.58, TIMP-1: t=11.29, TIMP-2: t=7.52, P<0.001) , which indi...