Caco-2细胞中二甲双胍的摄取和转运特征  

Uptake and transport characteristics of metformin in Caco-2 cell line

作　　者：王元佩[1] 张桂春[1] 孙丽娟[1] 胡金锋[1] 赵政[1] 

机构地区：[1]教育部和上海市脑功能基因组学重点实验室华东师范大学脑功能基因组学研究所,上海200062

出　　处：《中国药理学通报》2008年第12期1565-1569,共5页Chinese Pharmacological Bulletin

基　　金：上海市“浦江人才计划”资助项目(No05PJ14044);上海市“登山行动计划”重大资助项目(No06DZ19002)

摘　　要：目的从细胞和分子水平考察二甲双胍在Caco-2细胞上的摄取和通透性质,探讨二甲双胍与药物抵抗蛋白特别是P-gp的相互关系。方法HPLC方法对二甲双胍在Caco-2细胞摄取和通透性作定量分析;RT-PCR方法测定二甲双胍对MDR1基因表达的影响;钙黄绿素(calcein AM)测定体系考察二甲双胍与多药抗药性转运体(P-gp、MRP1和MRP2)的作用关系。结果二甲双胍在Caco-2细胞上摄取呈浓度相关性,且有较强通透性(Papp=2.86×10-6cm.s-1);二甲双胍摄取和转运不因P-gp特异性抑制剂维拉帕米存在与否而改变;二甲双胍能提高MDR1基因表达;对细胞中calcein水平无影响。结论二甲双胍在Caco-2细胞上易转运,不是P-gp底物,对MDR1表达有上调作用,对P-gp和MRPs无抑制作用。Aim To investigate the uptake, permeability and transport characteristics of metformin in Caco-2 cells at both cellular and molecuiar levels and the in teraction with the multidrug resistance-associated proteins, especially P-glycoprotein. Methods The uptake and permeability of metformin in Caco-2 cells were measured using HPLC; The effect of metformin on MDR1 mRNA expression was determined by RT-PCR; A calcein AM assay was used to evaluate the interaction between metformin and P-glycoprotein （P-gp） and muhidrug resistance-associated proteins （MRP1 and MRP2）. Results Mefformin was readily absorbed in a concentration-related manner and easily permeated in Caco-2 cells （Papp=2.86×10^-6cm·s^-1 ）. Co-incubation with verapamil did not alter the uptake and permeability of metformin. The expression of MDR1 in the cells was up-regulated by metformin,whereas it had no affect on calcein levels in Caco-2 cells. Conclusions Mefformin is well-permeable cross Caco-2 monolayers. The drug isn＇t a P-gp substrate., and has a role in upregulation of MDR1 expression. Metformin has no inhibitory effect on overall functions of P-pg and MRPs.

关 键 词：二甲双胍 摄取 转运 P-糖蛋白 MDR1 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]