山姜素激活孕烷X受体和上调CYP3A4 mRNA转录的研究  

Alpinetin activates PXR and up-regulates CYP3A4 mRNA

作　　者：窦薇[1,2] 丁丽丽[1] 张晶晶[1] 王峥涛[1,2] 

机构地区：[1]上海中医药大学中药研究所中药标准化教育部重点实验室暨上海市复方中药重点实验室,上海201203 [2]上海中药标准化研究中心,上海201203

出　　处：《中国药理学通报》2012年第6期761-763,共3页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No U1032604;81150040)

摘　　要：目的探讨山姜素能否通过活化孕烷X受体(PXR)诱导CYP3A4的转录表达及对CYP3A4 mRNA的实际诱导作用。方法在人结肠癌LS174T细胞中,用瞬时共转染报告基因实验研究山姜素(1～50μmol.L-1)对PXR介导的CYP3A4基因的转录激活;用荧光定量RT-PCR方法检测其对CYP3A4 mRNA的实际诱导。结果 10μmol.L-1浓度山姜素能够通过活化PXR诱导CYP3A4的转录(1.63倍);10和20μmol.L-1山姜素能够明显上调CYP3A4 mRNA(2.28倍和1.65倍)的表达。结论 PXR途径也许是山姜素诱导CYP3A4基因表达的调控因素之一。Aim To investigate the effects of alpinetin on pregnane x receptor（PXR） mediated transcriptional activation of CYP3A4 and the influence on CYP3A4 mRNA expression in LS174T cells.Methods Transient cotransfection reporter assays were performed in LS174T cells following alpinetin（1～50 μmol·L-1） treatment and the CYP3A4 activation was confirmed by measuring the activity of luciferase.CYP3A4 mRNA expression was assayed by real-time PCR.Results Alpinetin at 10 μmol·L-1 significantly transactivated the CYP3A4 reporter constructed in LS174T cells（1.63-fold）.The CYP3A4 mRNA expression was markedly increased（2.28-fold and 1.65-fold） by alpinetin at 10 μmol·L-1 and 20 μmol·L-1 respectively.Conclusion Activation of the PXR pathway might played a role in the up-regulation of CYP3A4 mRNA.

关 键 词：孕烷X受体 CYP3A4 共转染 mRNA 调节 山姜素 

分 类 号：R282.71[医药卫生—中药学]