几种药物对HepG2细胞MRP2表达的影响  

Effect of dexamethasone,phenobarbital and glutathione on expression of multidrug resistance- associated protein2 in HepG2 cells

作　　者：刘磊[1] 邓敏[2] 高人焘[1] 蔡淑清[2] 

机构地区：[1]安徽省立医院感染病科,230001 [2]华中科技大学同济医学院附属协和医院传染病科

出　　处：《实用肝脏病杂志》2006年第6期333-336,共4页Journal of Practical Hepatology

摘　　要：目的探讨还原型谷胱甘肽、苯巴比妥、地塞米松对人肝癌HepG2细胞细胞膜上MRP2 mRNA表达的影响,以探讨这些药物消退黄疸的作用机制。方法采用人肝癌HepG2细胞系作传代培养,并分别加入1000nM地塞米松、10mM还原型谷胱甘肽、0.15mM苯巴比妥和生理盐水作用48h后提取各组细胞的总mRNA,然后以同种药物同组内的β-肌动蛋白的基因表达量做为内对照,用逆转录-聚合酶链反应(RT-PCR)法检测,以光密度比值(MRP2/-βactin)半定量表示各组细胞MRP2 mRNA加药后表达的变化,将结果建立数据库进行方差分析和q检验。结果苯巴比妥组和地塞米松组的HepG2细胞MRP2 mRNA表达量都明显高于生理盐水组(P<0.01),并且地塞米松组MRP2 mRNA表达要明显高于苯巴比妥组(P<0.01),而谷胱甘肽组MRP2 mRNA表达要低于生理盐水对照组(P<0.05)。结论苯巴比妥、地塞米松可上调MRP2 mRNA的表达,由于MRP2为结合型胆红素运输的载体,因此上调MRP2 mRNA的表达可能为这两种药物促进结合型胆红素排泄,消退黄疸的作用机理之一。而谷胱甘肽作为MRP2的底物,它并不能促进MRP2的表达,谷胱甘肽对结合型胆红素向胆管内运输可能无作用。我们认为MRP2的表达水平可以作为结合型胆红素增高性疾病退黄药物治疗的评价指标之一,并加以开发。Objective This study intends to approaeh the mechanism of action of glutathione, phenobarbital or dexamethasone through examining the expression of muhidrug resistanceassociated protein 2 （MRP2） in HepG2 cells. Method HepG2 cells were cultured with dexamethasone （1000 nM）, glutathione （10mAM） and phenobarbital （0. 15mM） respectively for 48 h. Then we extracted the total RNA from each group and amplificated the mRNA of MRP2 and β-actin by RT PCR. We used MRP2/β-actin to demonstrate the change of the mRNA expression of MRP2 and analyze the result with analysis of variance and q test. Results Cells cultured for 48 h with dexamethasone or phenobarbital expressed more MRP2 mRNA （P〈0. 01）, while cells cultured with glutathione expressed few MRP2 mRNA （P〈0. 05）. Cells cultured with dexamethasone expressed more MRP2 mRNA than phenobarbital significantly （P〈0. 01）. Conclusion Dexamethasone and phenobarbital can up-regulate the expression of MRP2 mRNA , which may be one of processes of eliminating jaundice. Glutathione is the substrate of MRP2, but glutathione can not up-regulate the expression of MRP2 mRNA.

关 键 词：MRP2 谷胱甘肽 苯巴比妥 地塞米松 HEPG2细胞 

分 类 号：R735.7[医药卫生—肿瘤]