【摘要】 目的 观察银杏叶提取物(EGB)对大鼠肝纤维化的防治效果，探讨 EGB 抗肝纤维化的机 制。方法 采用四氯化碳诱导大鼠肝纤维化。EGB 各组四氯化碳处理同模型组，另分别给予0．25、0．5、 1．0g/kg EGB 灌胃。8周末检测其肝功能以及血清透明质酸和层黏连蛋白。取肝组织进行氧化应激测定，免 疫组织化学法检测核因子-kB(NF-kB)P65和α-平滑肌肌动蛋白的表达，逆转录聚合酶链反应法检 测转化生长因子β1(TGF β1)和Ⅰ型胶原 mRNA 的表达，凝胶电泳迁移率分析检测 NF-kB 的活性，并 进行病理组织学检查。结果 EGB 组肝纤维化分级评分、肝功能以及血清透明质酸和层黏连蛋白较模型组 明显改善；EGB 能抑制氧化应激、肝星状细胞的活化、NF-kB P65的表达以及 NF-kB 活性。此外，EGB 还可减低 TGF β1和Ⅰ型胶原 mRNA 的表达。结论 ECB 可能通过抑制氧化应激和 TGF β1的表达，减弱 NF-kB 诱导的肝星状细胞活化，从而阻止四氯化碳诱导的大鼠肝纤维化的发生发展。更多还原

【Abstract】 Objective To evaluate the effects of Ginkgo biloba extract（EGB）on CCl₄-induced liver fibrosis and to investigate the underlying mechanisms.Methods Rats were divided into the following groups:normal control group, CC1₄ model group,low dose EGB group,moderate dose EGB group and high dose EGB group.The rat liver fibrosis model was induced by intraperitoneal injection of CC1₄ twice a week for 8 weeks.The rats of the three EGB treated groups were given 0.25 g/kg,0.5 g/kg,1.0 g/kg of EGB through stomach tubes every day.At the end of the eighth week,blood and liver specimens were obtained.The expressions of nuclear factor kappaB（NF-κB）P65,and α-smooth muscle actin（α- SMA）were detected by immunohistochemistry.Radioimmunoassay was used to evaluate serum hyaluronic acid（HA）and laminin（LN）levels.Electrophoretic mobility shift assay（EMSA）was used to confirm the nuclear translocation activity of NF-κB in liver tissues.The mRNA expression of transforming growth factor-β1（TGFβ1）and collagen I were determined by RT-PCR.Malondialdehyde（MDA）,superoxide dismutase（SOD）and glutathione peroxidase（GSH-Px）in liver tissues and alanine aminotransferase（ALT）and aspartate aminotransferase（AST）in the sera were also examined. Results CC1₄ administration induced liver fibrosis,which was inhibited by EGB in a dose-dependent manner.The histopathologic scores of liver fibrosis,the levels of serum ALT,AST,HA and LN were significantly lower in the rats treated with EGB compared with those of the model group（P＜0.01 or P＜0.05）.SOD and GSH-Px activites were notably elevated and MDA content was significantly lower in the rats treated with EGB（P＜0.01 or P＜0.05）,indicating reduced oxidative stress.Immunohistochemical staining demonstrated inhibition of hepatic stellate cell（HSC）activation（in terms of α-SMA expression）and NF-κB P65 expression in the livers of the EGB-treated rats.As determined by EMSA and RT-PCR,activation of NF-κB,the mRNA expression of TGFβ1 and collagen I were significantly higher in model group rats.but obviously lower in EGB treated rats.Conclusion EGB is able to ameliorate liver injury and prevent rats from CCl₄-induced liver fibrosis by suppressing oxidative stress This process may be related to inhibiting the expression of TGFβ1 and the induction of NF-κB on HSC activation.更多还原