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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1.2~1.23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_(E1)mRNA的表达下调了0.6倍(P<0.01);SGI中剂量和高剂量组的CYP1_(A2)mRNA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_(D22)mRNA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。
Objective: To study the effects of Shenxiong glucose injection (SGI) on cytochrome P450 2_ (E1) (CYP2_ (E1)), 2_ (A11) (CYP2_ (A11)) and 1_ (A2) (A2)) and 2_ (D22) (CYP2_ (D22)) activity and mRNA expression levels. Methods: Kunming mice were randomly divided into normal group, phenobarbital group (0.70 g · kg -1), SGI low, medium and high dose groups (13.0, 19.5, 26.0 g · kg -1, 1)). The mice in each group were injected intravenously once a day for 7 days and then sacrificed. The liver microsomes were prepared for in vitro metabolism experiments, and the enzyme activities of CYP2_ (E1), CYP2_ (D22), CYP1_ (A2) and CYP3A were determined. The expression of CYP2_ (E1), CYP2_ (D22), CYP1_ (A2) and CYP2_ (A11) mRNA in liver tissues of mice were quantitatively analyzed by real-time fluorescence quantitative polymerase chain reaction q PCR. Results: Compared with the normal group, there was no significant difference in the liver index of each administration group. In vitro metabolism experiments showed that high dose of SGI down-regulated the activity of CYP2_ (E1) by 0.45-fold (P <0.05) compared with the normal group. SGI of middle dose and high dose of SGI upregulated the activity of CYP1_ (A2) by 1.2-1.23 <0.05), while SGI had no significant effect on the activity of CYP3A and CYP2_ (D22). qPCR analysis showed that CYP2_ (E1) mRNA expression was down-regulated 0.6-fold (P <0.01) in high-dose SGI group compared with normal group; the expression of CYP1_ (A2) mRNA in SGI middle- Times and 2.6 times (P <0.05) respectively. There was no significant difference in the expression of CYP2_ (A11) and CYP2_ (D22) mRNA between SGI group and normal group. Conclusion: SGI at medium and high doses can up-regulate the expression of CYP1_ (A2) in liver and induce the activity of liver CYP1_ (A2) in mice. However, high doses of SGI could down-regulate the expression of CYP2_ (E1) and inhibit the activity of liver CYP2_ (E1) in mice.