银杏叶提取物对实验性肝纤维化形成和逆转中TIMP-2表达的影响

Effect of Ginkgo biloba extract on tissue inhibitor-2 of metalloproteinase in CCl_4-induced liver damage in rats

目的 研究银杏叶提取物对大鼠肝纤维化形成和逆转的影响及其可能的机制。方法 应用CCl4诱导大鼠肝纤维化模型 ,同时 /造模完成后给予银杏叶提取物干预肝纤维化的发生和逆转 ,应用H&E、Masson和Gordon Sweet染色观察肝组织病理纤维化分级 ,生化法检测肝功能指标 ,RT PCR法测定肝组织中金属蛋白酶组织抑制因子 2 (TIMP 2 )表达 ,免疫组化法检测肝组织中αSMA表达。结果 给予银杏叶提取物可以显著降低大鼠肝纤维化程度 (P <0 .0 5 )和促进肝纤维化的逆转 (P <0 .0 5 ) ,改善肝功能 (P <0 .0 5 ) ,降低肝纤维化形成和恢复过程中肝组织TIMP 2的表达 (P <0 .0 5 ) ,使αSMA阳性细胞数减少 (P <0 .0 5 )。结论 银杏叶提取物可有效预防大鼠CCl4肝纤维化的形成并促进肝纤维化的逆转 ,可能与银杏叶提取物抗抑制TIMP 2表达、抑制肝脏星状细胞活化 /促进活化星状细胞凋亡有关。

Objective To assess the effect of Ginkgo biloba extract (GbE) on the development and reversibility of lives fibrosis in rats and to determine whether GbE has the effect of antifibrogenesis. Methods The model of CCl4-induced liver fibrosis was established in rats and treated with GbE at the same time or after confirmation of liver fibrosis. Liver tissue samples were used for histopathological examinations (H&E, Masson and Gordon-Sweet staining) and RT-PCR for expression of tissue inhibitor-2 of metalloproteinase. Blood samples were collected for determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST). The expression of αSMA in liver samples was also examined with immunohistochemistry.Results Liver fibrosis and expression of αSMA in GbE group was significantly decreased(P<0.05).The level of ALT, AST, and TIMP-2 was significantly decrease in GbE group(P<0.01).Conclusion GbE has protective effect on liver injury and can inhibit liver fibrosis and decrease liver fibrosis induced by CCl4 in rats. The mechanisms possibly contribute to effect of inhibiting TIMP-2 and suppressing the activation promoting the apoptosis of hepatic stellate cells (HSC).