银杏叶提取物对实验性大鼠肝纤维化的逆转作用

Experimental study on ginkgo bibloba extract reversing carbon tetrachloride-induced liver fibrosis in rats

[目的]观察银杏叶提取物(EGb)对四氯化碳(CCl4)诱导大鼠肝纤维化病理过程的逆转作用。[方法]采用CCl4腹腔注射诱导大鼠肝纤维化模型成功后,予EGb或0.85%氯化钠灌胃,8周后用苏木精伊红染色、苦味酸酸性品红染色和网状纤维染色观察大鼠肝脏病理变化,酶动力法检测肝功能,SP免疫组化法检测肝组织中α肌动蛋白(αSMA)、转化生长因子β1(TGFβ1)、I型胶原表达的变化,RT PCR法检测肝组织中TGFβ1、I型胶原、金属蛋白酶组织抑制因子(TIMP1)的表达情况。[结果]EGb可促进大鼠肝纤维化的逆转,使肝组织中αSMA、TGFβ1、I型胶原、TIMP1的表达降低(P<0.01);肝功能改善(P<0.01);肝组织纤维化程度分级好转,胶原纤维、网状纤维所占面积显著缩小(P<0.01)。[结论]EGb能有效逆转大鼠肝纤维化病理过程,其作用机制为抗脂质过氧化、保护肝细胞和抑制肝星状细胞活化,抑制TGFβ1、I型胶原、TIMP1的合成,从而逆转纤维化的形成。

Objective] To study the effect of ginkgo bibloba extract (EGb) ,an antioxidant, on liver fibrosis in rats . [Methods] The experimental hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl_4). EGb was administrated to the treatment group for 8 weeks. Control group received saline. Changes of liver pathology,liver function were compared. Expression of α-SMA, TGF-β_1 and collagen type I in the liver tissue were measured by SP immunohistochemistry method. Expression of TGF-β_1, collagen type I and TIMP_1 mRNA were tested by RT-PCR. [Results] Compared with the model group, in the treatment group the expression of α-SMA, TGF-β_1, collagen type I and TIMP_1 reduced ( P<0.01), liver function improved ( P<0.01), fibrosis degree of the liver ameliorated and the areas of collagen fiber and reticulum fiber decreased obviously ( P<0.01).[Conclusion]EGb could reverse the pathologic development of fibrosis. The mechanism possibly contributed to its anti-lipoperoxidation and hepatocyte protection effect, suppressing the activation of hepatic stellate cells and the synthesis of TGF-β_1, collagen type I and TIMP_1.