【摘要】 目的:观察几种植物化学物是否能通过活化孕烷X受体(PXR)诱导细胞色素P 4503A 4(CYP 3A 4)的转录表达。方法:在人肝肿瘤细胞株H epG2细胞中,用瞬时共转染报告基因实验进行异鼠李素、大豆异黄酮、木犀草素、姜黄素和芦丁素共5种植物化学物在不同浓度和不同处理时间下对PXR介导的CYP 3A 4的转录调节作用研究。结果:5种植物化学物分别作用于H epG2细胞24 h后,大豆异黄酮、木犀草素、姜黄素均能诱导PXR介导的CYP 3A 4基因的转录表达,诱导能力随浓度增强,而异鼠李素和芦丁素无类似作用。大豆异黄酮、木犀草素、姜黄素均能在1~50μm o l/L浓度之间诱导CYP 3A 4的转录表达,这3种植物化学物在50μm o l/L浓度时,诱导倍数分别为0.1%DM SO处理细胞的5.46倍、2.87倍和2.07倍。在不同处理时间的研究中,10μm o l/L和50μm o l/L大豆异黄酮、木犀草素和姜黄素均能在12 h~48 h内增强CYP 3A 4的转录表达,诱导能力随时间延长呈增强趋势。50μm o l/L大豆异黄酮、木犀草素和姜黄素作用H epG2细胞48 h后,诱导倍数分别为0.1%DM SO处理细胞的6.72倍、3.24倍和2.13倍。结论:植物化学物大豆异黄酮、木犀草素和姜黄素能通过活化PXR诱导CYP 3A 4的转录表达,异鼠李素和芦丁素则没有类似作用。更多还原

【Abstract】 Objective: To test the effect on human pregnane X receptor（hPXR）-mediated transcription regulation of CYP3A4 by five selected phytochemicals.Methods: Transient cotransfection reporter gene assays in HepG₂ cells were performed with the hPXR expression plasmid and the reporter gene plasmid which contains XRE in the promoter of CYP3A4 linked to luciferase.Results: In the dose-effect study,soybean isoflavone,luteolin and curcumin induced the CYP3A4 transcription via PXR in an evident dose-dependent manner,but isorhamnetin and rutin did not.The inducibility of soybean isoflavone,luteolin and curcumin was also increased in concentrations between 1 μmol/L and 50 μmol/L,24 h after induction,50 μmol/L soybean isoflavone,luteolin and curcumin exhibited a （5.46）-fold,2.87-fold,and 2.07-fold increase respectively,compared with 0.1% DMSO treated cells.In the time-effect study,10 μmol/L and 50 μmol/L soybean isoflavone,luteolin and curcumin induced CYP3A4 transcription between 12 h and 48 h,the strongest induction appeared in 48 h.48 h after induction,50 μmol/L soybean isoflavone,luteolin and curcumin exhibited a 6.72-fold,3.24fold,and 2.13-fold increase respectively,compared with 0.1% DMSO treated cells.Conclusion: Three phytochemicals,i.e.soybeam isoflavone,luteolin and curcumin stimulate the PXR-mediated transcription of CYP3A4.Isorhamnetin and rutin have no effect on the CYP3A4 transcription via PXR.更多还原