【摘要】 目的研究真菌性雌激素玉米赤霉烯酮(ZEA)是否能通过活化人甾体激素和外源化学物受体(SXR)诱导细胞色素P4503A4(CYP3A4)的转录表达。方法在人肝肿瘤细胞株细胞中,用瞬时共转染报告基因试验即共转染含人SXR序列质粒和含CYP3A4外源化学物反应元件的报告基因质粒来检测ZEA对SXR介导的CYP3A4的转录调节作用。结果ZEA能通过活化SXR诱导CYP3A4的转录表达,并具有剂量效应关系和时间效应关系。在剂量效应关系研究中,ZEA浓度分别为001、010、100和1000μmol/L时,其诱导倍数分别为01%二甲基亚砜处理细胞的(150±021)倍、(166±027)倍、(304±082)倍和(396±116)倍。在时间效应关系研究中,100和1000μmol/L的ZEA处理细胞48h后,诱导能力分别为01%二甲基亚砜处理细胞的(369±134)倍和(518±150)倍。在浓度为10μmol/L,处理时间为48h时诱导能力最大,为用01%二甲基亚砜处理细胞的(518±150)倍。结论ZEA能通过活化SXR诱导CYP3A4的转录表达。ZEA对CYP3A4的诱导可能影响其他CYP3A4底物,尤其是药物在体内的代谢。更多还原

【Abstract】 Objective To study whether zearalenone (ZEA), a fungal estrogen, can transcriptionally up rugulate the expression of cytochrome 450 3A4 (CYP3A4) transcription by activating human steroid hormone and xenobiotic receptor (SXR) Method Transient cotransfection reporter gene assays were performed with human SXR expression plasmid and a reporter plasmid contaning the SXR in the CYP3A4 gene promoter in HepG 2 cells Results The transcriptional induction of CYP3A4 by ZEA with a dose, time dependent manner ZEA at the concentrations of 0 01, 0 10, 1 00 and 10 00 μmol/L, respectively, could induce CYP3A4 with (1 50±0 21), (1 66±0 27), (3 04±0 82) and (3 96±1 16) folds, as compared with 0 1% DMSO Results from a time dependent study show that 1 00 and 10 00 μmol/L of ZEA for 12 to 48 hours could enhance the transcription of CYP3A4 with (3 69±1 34) and (5 18±1 50) folds, and 10 00 μmol/L of ZEA for 48 hours could induce the CYP3A4 gene expression (5 18±1 50) folds, as compared with 0 1% DMSO by activating human SXR Conclusion ZEA could induce the expression of the CYP3A4 gene transcription through activating SXR, possibly by affecting the other substrates of the CYP3A4, especially affecting the metabolism of drugs in the body更多还原