苦参碱对人孕烷X受体介导的CYP3A4调节及药物相互作用分析  

Study on the Effect of Matrine on CYP3A4 Through Human Pregnane X Receptor in vitro

作　　者：古月瑜[1] 廖晓忠 刘嘉辉[1] 陈玉玲 林美桂 张丽娜[4] 莫穗林[1] 

机构地区：[1]中山大学附属第一医院中医科,广东广州510080 [2]澳门镜湖医院 [3]广州市荔湾区石围塘街社区卫生服务中心,广东广州510360 [4]中山大学附属第六医院中医科,广东广州510655

出　　处：《中药材》2017年第3期684-688,共5页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金面上项目(81274135)

摘　　要：目的:研究苦参碱(Matrine)对CYP3A4转录激活、mRNA诱导作用的影响,并对其在联合用药中药物的相互作用进行评价。方法:利用CCK-8方法检测苦参碱对人结直肠癌LS174T细胞、人肝癌Hep G2细胞增殖的影响;瞬时共转染报告基因方法检测苦参碱对人孕烷X受体(PXR)介导的CYP3A4荧光素酶活性影响;Real-time PCR检测苦参碱对人孕烷X受体、CYP3A4 mRNA诱导作用影响。结果:在一定的浓度范围内,苦参碱对Hep G2和LS174T细胞的增殖均具有抑制作用;在Hep G2细胞中,苦参碱可通过激活PXR而诱导CYP3A4转录,并通过诱导PXR mRNA表达进而上调CYP3A4 mRNA表达。在LS174T细胞中,苦参碱可通过激活PXR诱导CYP3A4转录,并通过诱导PXR mRNA表达进而上调CYP3A4 mRNA表达,且其作用呈浓度依赖性。结论:苦参碱对CYP3A4的诱导可能与人孕烷X受体通路有关,与其他药物联合使用时有可能干扰其他药物的代谢。Objective：To investigate the effect of Matrine on CYP3A4 in transcriptional activation and the induction,and to evalu- ate the interaction of herb-drug in combination. Methods ：The cells proliferation effect of Matrine on LS174T and HepG2 cells was deter- mined by CCK-8 assay. Matrine affected on CYP3A4 through human preguane X receptor transfected into cells and luciferase activities were measured by ransient co-transfection reporter gene assay. Real-time PCR was applied to determine the mRNA expression of preg- nane X receptor and CYP3A4 in LS174T and HepG2 cells. Results：In a certain concentration range of Matrine, there was an obvious an- ti-proliferative effects on HepG2 and LS174T cells. For HepG2 cells, Matrine could induce CYP3A4 transcription by activating human pregnane X receptor, and induce mRNA expression of pregnane X receptor to up-regulate the mRNA expression of CYP3A4. For LS174T cells, Matrine could induce CYP3A4 transcription by activating human pregnane X receptor, and induce mRNA expression of pregnane X receptor to up-regulate the mRNA expression of CYP3A4, the action was in concentration dependent. Conclusion：The effect of Ma- trine on CYP3A4 maybe relate to the activation of preguane X receptor,which indicate that Matrine might has an influence on the me- tabolism with other drugs in combination.

关 键 词：苦参碱 孕烷X受体 CYP3A4 药物相互作用 

分 类 号：R285.5[医药卫生—中药学]