目的拟黑多刺蚁乙醇提取物石油醚部位对大鼠肝微粒体细胞色素P450酶的影响。方法健康SD雄性大鼠随机分为6组,拟黑多刺蚁乙醇提取物石油醚部位低、中、高3个剂量组(实验组,分别相当于药材1,2,4 g·kg^-1)、地塞米松阳性对照组、苯巴比妥阳性对照组、空白对照组,每组3只。实验组大鼠分别灌胃给予拟黑多刺蚁乙醇提取物石油醚部位低、中、高3个剂量,每天一次,连续10 d;地塞米松阳性对照组大鼠腹腔给予地塞米松100 mg·kg^-1,每天一次,连续4 d;苯巴比妥阳性对照组大鼠腹腔给予苯巴比妥80 mg·kg^-1,每天一次,连续3 d;空白对照组大鼠给予等量0.9%氯化钠,均灌胃给药,每天一次,连续10 d。取肝组织,用液质联用、荧光高效液相色谱、反转录-聚合酶链反应、免疫印迹杂交方法分别检测细胞色素P450酶活性,基因表达和蛋白表达的变化。结果拟黑多刺蚁乙醇提取物石油醚部位低、中、高剂量均能显著性提高CYP1A2 mRNA水平、蛋白表达水平以及酶活性,且呈剂量依赖性。结论拟黑多刺蚁乙醇提取物石油醚部位对大鼠CYP1A2有诱导作用,提示其可能与CYP1A2底物、诱导剂或抑制剂发生药物相互作用。
Objective To study the effect of the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger with antigout activity on liver microsomal cytochrome P450 in rats. Methods Healthy male SD rats were randomly divided into six groups( 3 rats of each group) : three groups of the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger( test groups,the low dose group,the middle dose group and the high dose group with equivalent to 1,2,4 g·kg^- 1,respectively),two positive control groups and one blank control group. The rats in the low dose,the middle dose and the high dose test groups were administered daily by gavage at corresponding dose of the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger for 10 consecutive days. The rats in positive control groups were treated by dexamethasone( 100 mg · kg^- 1· d^- 1,ip,daily for 4 days) or phenobarbital( 80mg·kg^- 1· d^- 1,ip,daily for 3 days). Blank control rats received equivalent volume of sterile normal saline daily by gavage for 10 consecutive days. The levels of CYP450 activity,mRNA,protein in rat liver microsome were analyzed by LC / MS / MS or RP- HPLC- FLD,RT- PCR,Western blot,respectively. Results CYP1A2 activity,protein expression and mRNA levels were increased significantly in a dose- dependent manner with the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger at low,middle and high dose,respectively. Conclusion The petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger can induce CYP1A2 in rats,suggesting the potential of drug- drug interactions between the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger and the inducers,inhibitors,or substrates of CYP1A2.