银杏内酯对CCl_4诱导的小鼠肝损伤的作用研究

Effects of ginkgolide on carbon tetrachloride-induced hepatic injury in mice

目的探讨银杏内酯对CCl4诱导的小鼠肝损伤的保护作用及其机制。方法随机将50只SD小鼠分为5组,分别为空白对照组、模型组、银杏内酯低剂量组、银杏内酯中剂量组和银杏内酯高剂量组。采用CCl4腹腔注射和灌胃制作小鼠肝损伤模型。通过观察肝脏的解剖学形态,检测血丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平来评估银杏内酯对小鼠肝脏的保护作用。Real time-PCR检测孕烷X受体(PXR)、CYP3A11、CYP3A13和RXRα的表达。结果与空白对照组相比,模型组小鼠肝脏表面粗糙、轮廓萎缩;血清ALT和AST水平明显升高。与模型组相比,银杏内酯组小鼠肝脏表面光滑、轮廓清晰;血清ALT和AST水平明显降低,肝脏PXR、RXRα、CYP3A13和CYP3A11表达水平明显升高。结论银杏内酯对CCl4诱导的小鼠肝损伤有一定的保护和修复作用,其保护效果呈明显剂量依赖性。PXR、RXRα、CYP3A13、CYP3A11基因表达的上调可能在小鼠肝损伤保护中起重要作用。

Objective To investigate the protective effects of ginkgolide on carbon tetrachloride （CC14）-induced hepatic injury in mice and discuss its mechanism. Methods 50 SD mice were randomly divided into five groups： control group, model group, small, middle and large dosage of ginkgolide group. The model of hepatic injury was established through intragastric administration and injection with CC14. The protective effects of ginkgolide on hepatic injury in mice were evaluated by observing morphology and pathological section of liver, and detecting the activities of ALT and AST. PXR, RXRot, CYP3A13 and CYP3A11 were detected by Real time-PCR. Results Compared with the control group, livers of model group appeared rough surface and shrank contour, and the activity of serum ALT and AST increased signifi- cantly. While compared with model group, livers of ginkgolide groups appeared smooth surface and integral contour, the activity of serum ALT and AST decreased significantly, and levels of PXR, RXRoL, CYP3A13 and CYP3A11 in liver increased significantly. Conclusion Ginkgolide can prevent liver injury induced by CC14 in some extent, and the pro- tective effects is dose-dependant remarkably. It is suggested that upregulation of PXR, RXRc~, CYP3A13, CYP3A11 gene may play an important role in protection of hepatic injury in mice.