中文摘要：

目的 探讨盐酸川芎嗪对小鼠肝细胞色素P_（450）酶（CYPs）主要亚型及相关核受体的影响。方法 将小鼠分为5组：空白对照组、苯巴比妥组、盐酸川芎嗪小剂量（13.0 mg·kg^-1·d^-1）组、盐酸川芎嗪中剂量（19.5 mg·kg^-1·d^-1）组、盐酸川芎嗪大剂量（26.0 mg·kg^-1·d^-1）组,连续7 d给药。取5组小鼠的肝脏组织,制备肝微粒体、提取RNA,检测5组小鼠CYP活性、mRNA水平和蛋白表达的变化。结果 与空白对照组比较,盐酸川芎嗪大剂量组CYP1A2酶活性、mRNA水平和蛋白表达分别上调1.43,1.44和1.40倍（P〈0.05）。盐酸川芎嗪组CYP2E1、CYP2D22、CYP3A的酶活性、mRNA水平与空白对照组比较,均差异无统计学意义。与空白对照组比较,盐酸川芎嗪大剂量组AhR mRNA水平上调1.6倍（P〈0.05）。盐酸川芎嗪对HNF-4α、PXR和PPARα的mRNA水平无显著影响。随着盐酸川芎嗪的剂量增高,CYP2E1蛋白表达有上升趋势,但无显著性影响。结论 盐酸川芎嗪对小鼠体内肝CYP2E1、CYP2D22、CYP3A、HNF-4α、PXR和PPARα无显著影响,但对CYP1A2活性有诱导作用,该作用很可能与盐酸川芎嗪上调AhR水平从而促进CYP1A2表达有关。

英文摘要：

Objective To investigate the influence of ligustrazine hydrochloride on cytochrome P450 and nuclear receptor in hepatocyte of mice. Methods Mice were randomly divided into blank control group, phenobarbital group, and ligustrazine hydrochloride low-, medium- and high-dose groups （13.0,19.5 and 26. 0 mg ·kg^-1·d^-1）. Then the mice were sacrificed after were administered medicines once daily for consecutive 7 days. Liver microsomes were prepared to determine the enzyme activities. Quantitative real-time PCR and Western blotting was employed to examine the expression of these four CYP450 enzymes and nuclear receptor in liver tissue of mice. Results Compared with the blank control group, CYP1A2 activity, mRNA and protein expression were increased by 1.43,1.44 and 1.40 times （ P 〈 0 .0 5 ） respectively in the ligustrazine hydrochloride dose group. Ligustrazine hydrochloride was found to have no impact on the activities of CYP2E1 , CYP3A and CYP2D22. AhR mRNA was increased by 1.6 times （ P 〈 0. 05 ） in the ligustrazine hydrochloride dose group. Ligustrazine hydrochloride was found to have no impact on the expression of HNF-4α, PXR and PPARa. Conclusion Ligustrazine hydrochloride is found to have no impact on the expression of CYP2E1 , CYP2D22, CYP3A, HNF-4α, PXR and PPARa, but induces the activity of CYP1A2. This effect is likely to be related toin creasing AhR level to promote the expression of CYP1A2.