[关键词]
[摘要]
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/mL)的YQFM或特异性诱导剂(CYP1A2诱导剂:50 μmol/L奥美拉唑;CYP2B6诱导剂:1 000 μmol/L苯巴比妥;CYP3A4诱导剂:25 μmol/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 mRNA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mRNA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。
[Key word]
[Abstract]
Objective To evaluate the effect of Yiqi Fumai Lyophilized Injection (YQFM) on the drug metabolism enzyme CYP1A2, 2B6 and 3A4 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/mL) of YQFM or specific inducer (CYP1A2 inducer:50 μmol/L Omeprazole; CYP2B6 inducer:1 000 μmol/L Phenobarbital; CYP3A4 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 mRNA expression of CYP1A2, 2B6 and 3A4 was detected by fluorescent quantitative PCR. Results:YQFM showed no induction on CYP1A2, CYP2B6 and CYP3A4 enzyme activities and mRNA 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.
[中图分类号]
[基金项目]