祖师麻甲素在Caco-2细胞模型中的吸收机制研究

Mechanism of daphnetin absorption across Caco-2 monolayer model

目的:研究祖师麻甲素在Caco-2细胞模型中的吸收特性,为其及祖师麻给药途径的选择和剂型的合理设计提供依据。方法:采用Caco-2细胞单层模型研究祖师麻甲素的摄取和跨膜转运,采用HPLC法检测药物浓度,计算其表观渗透系数,考察时间、温度、pH值、药物浓度以及P-gp抑制剂对祖师麻甲素吸收的影响。结果:祖师麻甲素以被动扩散为主要方式被细胞摄取和转运。药物的摄取与时间、温度和浓度呈正相关,不受媒介pH值的影响。祖师麻甲素从Basolateral-Apical方向转运要稍快于相反方向。随着药物浓度的增加,比值呈降低趋势,但变化不大。P-gp抑制剂维拉帕米对祖师麻甲素的转运无显著性影响。结论:祖师麻甲素是以被动扩散为主要方式被小肠上皮细胞摄取和转运,此过程不受P-gp的外排作用。

Objective：To investigate the intestinal absorption of daphnetin and the mechanism using Caco-2 monolayer model.Methods：The Caco-2 cell monolayer model was used to study the bi-directional transport of daphnetin and the effects of time,temperature,pH,drug concentration and P-gp inhibitor on the daphnetin absorption.Drug concentration was measured by HPLC and the apparent permeability coefficients（Papp） were calculated.Results：The uptake and absorption of daphnetin were passive diffusion as the dominant process. The daphnetin uptake and absorption was not controlled by pH, but positively correlated to uptake time and temperature. Popp of basolateral to apical was slightly higher than that of apical to basolateral. The inhibitor of P-gp, verapamil, did not significantly enhance the uptake amount of daphnetin. Conclusion ： The passive diffusion is the major transport of daphnetin uptake and absorption by Caco-2 monolayer. P-gp has no efflux effects on the uptake and transepithelial transport of daphnetin.