异鼠李素对CYP3A4的调节及药物相互作用分析  

Effects of isorhamnetin on CYP3A4 and herb-drug interaction

作　　者：丁丽丽[1,2,3] 张晶晶[1,2,3] 窦薇[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及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 [3]中国药科大学生药学研究室,江苏南京210038

出　　处：《药学学报》2012年第8期1006-1010,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81150040,U1032604)

摘　　要：观察异鼠李素对CYP3A4的转录激活、mRNA诱导及酶活性的影响,并对其在联合用药中的药物相互作用进行评价。在HepG2细胞中,采用瞬时共转染报告基因实验检测异鼠李素对PXR介导的CYP3A4的转录激活作用;荧光定量RT-PCR方法检测其对CYP3A4 mRNA的诱导作用;底物化学发光法检测其对细胞CYP3A4酶活性的影响;细胞增殖实验检测其对化疗药物伊立替康肝癌细胞毒性的影响。结果表明,异鼠李素(1、10及25μmol·L 1)可以剂量依赖性通过激活PXR而诱导CYP3A4的转录,同时可剂量依赖性上调CYP3A4mRNA表达,但对CYP3A4酶活性无影响,对化疗药物伊立替康肝癌细胞毒作用也无影响。提示异鼠李素对CYP3A4 mRNA的诱导可能与PXR途径有关,并且可能不会干扰与其联用的其他药物的代谢。本研究可以为异鼠李素临床合理用药提供参考。The study is to report the investigation of the effects of isorhamnetin on CYP3A4 and herb-drug interaction.A reporter gene assay is used to test pregnane X receptor transactivation action,qRT-PCR and a luminescence-based assay were applied to determine mRNA induction and enzyme activity of CYP3A4 after isorhamnetin treatment.The interaction of irinotecan and isorhamnetin was assessed by inhibition assay of cell proliferation.Isorhamnetin at 1,10 and 25 μmol·L？1 transactivated the CYP3A4 reporter construct and upregulated CYP3A4 mRNA as well in a dose-dependent manner.However,isorhamnetin had no effect on enzyme activity of CYP3A4 and irinotecan HepG2 cytotoxicity.In conclusion,activation of PXR by isorhamnetin played a role in the upregulation of CYP3A4 mRNA.Moreover,joint action of isorhamnetin with other drugs may not be associated with the herb-drug interaction.

关 键 词：孕烷X受体 CYP3A4 药物相互作用 异鼠李素 

分 类 号：R963[医药卫生—微生物与生化药学]