【摘要】 目的:研究参芎葡萄糖注射液（Shenxiong glucose injection,SGI）对小鼠肝脏细胞色素P450 2_E1(CYP2_E1),2_A11(CYP2_A11),1_A2(CYP1_A2)和2_D22(CYP2_D22)酶活性以及mRNA表达水平的影响。方法:将昆明小鼠随机分为正常组,苯巴比妥组(0.70 g·kg^-1),以及SGI低、中、高剂量组(13.0,19.5,26.0 g·kg^-1)。各组小鼠每天尾静脉注射药物1次,连续注射7 d后处死。取其肝脏制备肝微粒体进行体外代谢实验,测定CYP2_E1,CYP2_D22,CYP1_A2和CYP3A的酶活性。并用实时荧光定量聚合酶链式反应q PCR技术定量分析小鼠肝组织中CYP2_E1,CYP2_D22,CYP1_A2和CYP2_A11的mRNA表达水平。结果:与正常组比较,各给药组小鼠肝指数没有显著差异。体外代谢实验表明,相较正常组,高剂量SGI能下调CYP2_E1酶活性0.45倍（P<0.05）;中剂量和高剂量的SGI可上调CYP1_A2酶活性1.2¹.23倍（P<0.05）;而SGI对CYP3A和CYP2_D22的活性无显著影响。q PCR分析发现,相较正常组,高剂量SGI组CYP2_E1mRNA的表达下调了0.6倍（P<0.01）;SGI中剂量和高剂量组的CYP1_A2mRNA的表达分别上调了1.7倍和2.6倍（P<0.05）。SGI组和正常组之间的CYP2_A11和CYP2_D22mRNA表达量无显著性差异。结论:中高剂量的SGI能上调小鼠肝CYP1_A2的表达,并诱导小鼠肝CYP1_A2的酶活性。而高剂量的SGI能下调小鼠肝CYP2_E1的表达,并抑制小鼠肝CYP2_E1的酶活性。更多还原

【Abstract】 Objective: To investigate the effects of Shenxiong glucose injection（ SGI） on the activities and mRNA expressions of hepatic cytochrome P450 2_E1(CYP2_E1),2_A11( CYP2_A11),1_A2( CYP1_A2) and 2_D22( CYP2_D22) in mice. Method: Kunming mice were randomly divided into normal group,hepatic microsomal enzyme inducer group,and SGI low dose,middle dose and high dose（ 13. 0,19. 5,26. 0 m L·kg- 1） groups. The mice were killed after medicines administration once a day for consecutive 7 days by tail intravenous injection.Liver microsomes were prepared for in vitro metabolism experiment to determine the enzyme activities of CYP2_E1,CYP2_D22,CYP1_A2 and CYP3A,and quantitative real-time PCR was employed to examine the mRNA expressions of these four CYP450 enzymes in liver tissues of mice. Result: There was no significant difference in the liver indexes between various treatment groups and normal group. In vitro metabolism experiment showed that, as compared with the normal group, CYP2_E1 activity was decreased by 0. 45 times in the SGI high dose group（ P < 0. 05）,and CYP1_A2 activities were increased by 1. 20-1. 23 times in the SGI middle dose and high dose groups（ P < 0. 05）. SGI was found to have no significant effect on the activities of CYP3 Aand CYP2_D22. The results of fluorescence quantitative PCR showed that,as compared with the normal group,CYP2_E1 mRNA expression was decreased by 0. 45 times in the SGI high dose group（ P < 0. 01）,and CYP1_A2 mRNA expressions were increased by 1. 7 times and 2. 6 times respectively in SGI middle dose and high dose groups（ P < 0. 05）. There was no significant difference between SGI groups and normal group in the mRNA expressions of CYP2_A11 and CYP2_D22.Conclusion: Middle dose and high dose SGI could up-regulate the hepatic CYP1_A2 mRNA expressions and induce the enzyme activity of CYP1_A2 in mice; high dose SGI could down-regulate the hepatic CYP1_A2 mRNA expressions and inhibit enzyme activity of CYP2_E1 in mice.更多还原