注射用益气复脉(冻干)对CYP450药物代谢酶1A2、2B6和3A4诱导作用的体外研究

In Vitro study of induction effects of Yiqi Fumai Lyophilized Injection on CYP450 metabolizing enzymes 1A2, 2B6 and 3A4

目的评价注射用益气复脉(冻干,YQFM)对人原代肝细胞中的药物代谢酶CYP1A2、2B6和3A4是否具有诱导作用。方法采用3个单供体的人原代肝细胞分别与不同质量浓度(0.026、0.260和2.600 mg/m L)的YQFM或特异性诱导剂(CYP1A2诱导剂:50μmol/L奥美拉唑;CYP2B6诱导剂:1 000μmol/L苯巴比妥;CYP3A4诱导剂:25μmol/L利福平)于37℃、5%CO2条件下共孵育3 d,液质联用技术(LC-MS/MS)检测酶活性,实时荧光定量PCR技术检测CYP1A2、2B6和3A4 m RNA表达量。结果 YQFM在测试浓度条件下对人原代肝细胞的CYP1A2、CYP2B6和CYP3A4的酶活性和m RNA的表达均无诱导作用。结论 YQFM不具有显著的基于药物代谢酶诱导的中药和化学药的相互作用。

Objective To evaluate the effect of Yiqi Fumai Lyophilized Injection（YQFM） on the drug metabolism enzyme CYP1 A2, 2 B6 and 3 A4 in human primary hepatocytes. Methods In this study, human primary hepatocytes were used from three individual donor, and incubated with different concentrations（0.026, 0.260 and 2.600 mg/m L） of YQFM or specific inducer（CYP1 A2 inducer： 50 μmol/L Omeprazole; CYP2 B6 inducer： 1 000 μmol/L Phenobarbital; CYP3 A4 inducer： 25 μmol/L Rifampicin）under condition of 37 ℃ and 5% CO2 for 3 d. The enzyme activity was determined by liquid chromatography-mass spectrometry（LC-MS/MS）, and m RNA expression of CYP1 A2, 2 B6 and 3 A4 was detected by fluorescent quantitative PCR. Results： YQFM showed no induction on CYP1 A2, CYP2 B6 and CYP3 A4 enzyme activities and m RNA expression in human primary hepatocytes under test concentration. Conclusion YQFM does not have a significant Herb-Drug Interaction（HDI） based on the induction of drug metabolism enzyme.