银杏叶提取物对肝纤维化大鼠肝脏低氧诱导因子1α及血管内皮生长因子表达的影响

Effect of Ginkgo Biloba extract on hypoxia-inducible factor 1α and vascular endothelial growth factor in rats with liver fibrosis

目的:观察银杏叶提取物(GbE)对肝纤维大鼠肝组织低氧诱导因子1α(HIF-1α)及血管内皮生长因子(VEGF)表达的影响,探讨GbE抗肝纤维的作用机制。方法:采用40%的CCl4皮下注射(3mL.kg-1.d-1,2次/周,首剂加倍),连续6周诱导大鼠肝纤维化模型,同时分别以高、中、低剂量(200、100、50mg.kg-1.d-1)GbE灌胃干预6周,常规HE和Masson染色观察大鼠肝组织炎症和纤维化程度,RT-PCR及免疫组化法检测肝组织HIF-1α和VEGF基因的mRNA及蛋白表达。结果:模型组大鼠肝组织炎症和纤维化程度计分较正常组明显增高(P<0.01),肝组织HIF-1α和VEGF基因的mRNA及蛋白的表达较正常组明显增强(P<0.05,P<0.01),HIF-1α蛋白表达水平与肝纤维化程度、VEGF mRNA表达水平呈明显的正相关;应用高、中、低剂量GbE干预后,大鼠肝组织炎症和纤维化程度显著减轻(P<0.05,P<0.01),肝组织HIF-1α和VEGF基因的mRNA及蛋白表达明显下降(P<0.05)。结论:GbE下调肝纤维化大鼠肝组织HIF-1α及其下游分子VEGF的转录和表达可能是其抗肝纤维化作用的机制之一。

Objective： To observe the effect of Ginkgo Biloba Extract（GbE） on hypoxia-inducible factor 1α（HIF-1α）and vascular endothelial growth factor（VEGF） in rats with liver fibrosis,and explore the mechanism of anti-hepatic fibrosis of GbE.Methods： The model of rat liver fibrosis was induced by subcutaneous injection of 40% CCl4,according to 3mL·kg-1·d-1,twice per week,The initial dose was doubled.Meanwhile,all the rats were dealed with different doses of GbE（200,100 and 50mg·kg-1·d-1） by gavage.After the experiment,the inflammation and fibrosis degree of rat were observed with HE and Masson dyeing,the mRNA and protein expressions of hepatic tissue HIF-1α,VEGF were detected with RT-PCR and immunohistochemical method.Results： The scorings of the inflammation and fibrosis degree in models were increased than the those of the normal,the mRNA and protein expressions of hepatic tissue HIF-1α,VEGF were enhanced than in the normal.The degree of HIF-1α protein expression obviously showed a positive correlation with fibrosis degree and VEGF mRNA expression.After the treatment of GbE,the inflammation and fibrosis degree were significantly reduced,the mRNA and protein expressions of hepatic tissue HIF-1α,VEGF were obviously decreased.Conclusion： the down regulating of GbE on transcription and expression of hepatic tissue HIF-1α and its downstream molecule VEG probably is one of its mechanism of anti-liver fibrosis.