芦丁在Caco-2细胞模型中吸收和外排机制的研究

Mechanism of Absorption and Effluxion of Rutin in Caco-2 Cell Model

利用Caco-2细胞模型研究芦丁在小肠上皮的摄取、跨膜转运及外排动力学机制,评价孵育时间、芦丁浓度、P-糖蛋白抑制剂环孢素A和多药耐药相关蛋白抑制剂维拉帕米对芦丁的细胞摄取与转运的影响。结果表明,药物摄取量与孵育时间、药物浓度呈正相关,环孢素A和维拉帕米对芦丁的细胞摄取量无显著影响(P>0.05)。不同浓度药物从基底侧(basolateral,BL)到肠腔侧(Apical,AP)的表观渗透系数P_(app.BL-AP)与AP到BL的P_(app.AP-BL)比值均在0.5～1.5。试验结果提示芦丁是以被动扩散为主要转运方式被小肠上皮细胞摄取和转运,且不受外排蛋白外排作用的影响。

The mechanism of uptake, transmembrane transport and effluxion of rutin was discussed with Caco-2 cell model. The effects of incubation time, drug concentration and two inhibitors （cyclosporine A and verapamil） on the uptake and transport of rutin were investigated. The uptake of rutin was positively correlated to incubation time and drug concentration. Cyclosporine A and verapamil had no significant influence on cellular uptake of rutin （P〉0.05）. Ratios of Papp of basolateral to apical and Papp of apical to basolateral under the condition of different drug concentrations were between 0.5 to 1.5. The results suggested that the enterocyte transport of rutin was passive diffusion and this process was not affected by efflux protein.