药物跨膜转运细胞模型影响因素及应用

本文详细介绍了Caco-2细胞系和MDCK细胞系的特点、跨膜转运细胞模型的建立及其影响因素,包括细胞模型的选择、细胞接种密度、细胞单层的紧密性等细胞因素和Transwell多微孔膜的性质等环境因素。概述了国内外关于利用Caco-2和MDCK细胞系作为模型进行药物筛选、药物相互作用和研究药物吸收转运机制等方面的内容及MDCK细胞模型作为肠道模型、肾脏模型及血脑屏障模型的应用。比较了Caco-2细胞和MDCK细胞在肠道模型方面的差别,MDCK细胞主要用于选择性研究药物在小肠吸收及转运机制,特别用于细胞旁被动转运药物的研究,而Caco-2细胞用于双向转运或能量依赖主动转运研究。MDCK细胞模型可在体外培养条件下平稳转染人类MDR1基因,因此可高表达P-gp基因,可作为可用于评估肾脏药物相互作用、快速进行候选药物筛选及研究药物转运机制的理想模型。

Important Applications and Influence Factors of cell Monolayers in the Study of the Drug Transport

This review introduces the characteristics and establishment of Caco-2 and MDCK cell line and summarizes the main influencing factors of drug transport. Cell factors contain the selection, tight junction and density of cell modes. Environment factor main is the performance of semi-permeable membranes. Caco-2 cell and MDCK cell could be used as a drug transport model are widely used in drug screenings, and the study of mechanisms of drug interaction and absorption or transport, as well as MDCK as models of intestinal mucosa, blood brain barrier and kidney. Comparison with the difference in model of intestinal mucosa between Caco-2 and MDCK cell, MDCK cell monolayer have been considered as an alternative for Caco-2 for studying absorption capacity and transport mechanisms of passive transport drugs in small intestine, especially for paracellular passive transport drugs. Caco-2 cells are used in the bidirectional transport and energy-dependent active transport study. MDCK cells are easy to culture and to transfect, and the high level of P-glycoprotein expression in MDR1-MDCK cells makes this a well-suited model for evaluating mechanisms of renal drug interactions and permeability screens.