【摘要】 目的:观察山奈酚能否通过活化孕烷X受体(PXR)诱导细胞色素P 450 3A 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试验检测山奈酚对PXR介导的CYP 3A 4的转录调节作用。结果:山奈酚能通过活化PXR诱导CYP 3A 4的转录表达,其诱导能力随山奈酚的浓度增大和处理时间延长而呈增强趋势。山奈酚在浓度为0.001、0.01、0.1、1.0和10.0μm o l/L下,其诱导倍数分别为0.1%二甲基亚砜(DM SO)处理组的(1.31±0.27)倍、(1.45±0.36)倍、(1.96±0.50)倍、(2.90±1.07)倍和(7.93±0.75)倍(P均<0.05)。1.0和10.0μm o l/L的山奈酚在48 h内其诱导作用随诱导时间的增加而增强,处理48 h后其诱导能力分别为0.1%DM SO处理组的(3.73±1.21)倍和(8.42±1.47)倍。结论:山奈酚能通过活化PXR诱导CYP 3A 4的转录表达。更多还原

【Abstract】 Objective: To investigate whether kaempferol stimulates pregnane X receptor（PXR）-mediated transcription of CYP3A4.Methods:Transient cotransfection reporter gene assay was performed with PXR expression plasmid and a reporter plasmid containing the XREs in the CYP3A4 gene promoter in HepG₂cells.Results:Kaempferol activated PXR-mediated transcription of CYP3A4 in a dose,time-dependent manner.In the dose-response study,kaempferol exposure at concentrations of 1.0×10^-3,1.0×10^-2,0.1,1.0 and 10.0 mol/L for 24 h increased CYP3A4 transcription by（1.31±0.27）,（1.45±0.36）,（1.96±0.50）,（2.90±1.07） and（7.93±0.75） fold,respectively compared with 0.1% DMSO（P<0.05）.The results from time-course study showed that after 48 h exposure 1.0 and 10.0 mol/L of kaempferol enhanced the transcription of CYP3A4 by（3.73±1.21） fold and（8.42±1.47） fold,respectively.Conclusion:Kaempferol may be a human CYP3A4 gene inducer through PXR,and may affect the metabolism of a large number of substrates of CYP3A4 simultaneously taken.更多还原