5-氨基水杨酸在Caco-2、L-MDR1和MRP2细胞中的转运研究

Study on transport of 5-aminosalicylate in Caco-2, L-MDR1 and MRP2 cell monolayers

目的：研究5-氨基水杨酸（5-ASA）的跨膜转运是否涉及P-糖蛋白和多药耐药蛋白（MRP2）。方法：以Caco-2、L-MDR1、MRP2等三种细胞为模型，测定5-ASA跨膜转运的转运率和表观渗透常数。此外还研究了5-ASA对地高辛在Caco-2细胞转运的影响。结果：在Caco-2、L-MDR1和MRP2细胞，5、50、500gmol·L^-1 5-ASA从底端（B）→顶端（A）方向和A→B方向的转运率和表观渗透系数（Papp）均无统计学差异（P〉0．05）。在Caco-2细胞，与未用5-ASA组相比，各浓度5-ASA组（50μmol·L^-1～5mmol·L^-1）对地高辛的Papp和B→A方向的净转运率无明显影响（P〉0．05）。结论：5-ASA可能不是P-糖蛋白和MRP2的底物，也不能提示5-ASA是P-糖蛋白的抑制剂或诱导剂。

AIM： To investigate whether P-glycoprotein and MRP2 are involved in transport of 5-aminosalieylate （ 5-ASA ）. METHODS： Permeability coefficients and transport rates of 5-ASA across Caco-2, L-MDR1 and MRP2 monolayers were measured. Trans epithelial transport of digoxin across Caco-2 monolayer with addition of 5-ASA was also studied. RESULTS： No differences of permeability coefficients and transport rates of 5-ASA at 5, 50 and 500 μmol·L^-1 between basal-to-apical and apical-to-basal direction were measurable across Caco-2, L-MDR1 and MRP2 monolayers （ P 〉 0.05 ）. Compared with control experiments, no significant differences were observed in basal-to-apical net transport and Papp of digoxin （5 μmol·L^-1） in the presence of 5-ASA （50 μmol· L^-1 - 5 mmol·L^- 1 ） （ p 〉 0.05 ）. CONCLUSION： 5-ASA can not be regarded as a substmte of P-gp or MRP2. Inhibition or induction of P-glycoprotein by 5- ASA could be excluded. Further studies are needed to identify the nature of the involved active carrier system（s） in intestinal secretion of 5-ASA.