基于Caco-2细胞模型研究蝙蝠葛碱的跨膜吸收机制

目的:研究蝙蝠葛碱在Caco-2细胞模型中的跨膜转运机制.方法:采用Caco-2细胞模型,进行A-B和B-A双向转运实验,计算表观渗透系数(Papp)、外排比率(ER)和累积转运量,考察蝙蝠葛碱不同质量浓度、细胞两侧pH梯度和螫合剂EGTA对蝙蝠葛碱转运的影响.结果:高、中、低浓度下的ER分别为1.11,4.49和7.24,即中、低浓度下转运有明显极化现象；顶侧pH 7.4和6.5时,ER值分别为3.95和9.38,即pH梯度存在时,蝙蝠葛碱吸收减少,外排增加；加入螯合剂EGTA后,Papp,ER和累积转运量均无显著改变.结论:蝙蝠葛碱的吸收有主动转运机制存在；pH梯度能驱动了蝙蝠葛碱的外排转运,偏碱性环境较酸性环境易于吸收；其吸收途径主要为跨细胞通道转运.

Absorption Mechanism of Dauricine based on Caco-2 Cell Line

Objective: To investigate the absorption mechanism of dauricine based on Caco-2 cell line. Method : Bidirectional transport of dauricine in Caco-2 cell model was used; apparent permeability coefficients(P_app), efflux ratio(ER) and accumulation transport amount were calculated; the effect of drug concentration ,pH gradient and EGTA on the bidirectional transport of dauricine were studied. Result : At high, middle and low concentrations the efflux ratio (ER) was 1.11,4.49, 7.24 respectively, so there was significant polar phenomenon for transport of dauricine; at apical lateral when pH was 7.4 and 6.5,ER were 3.95 and 9.38 respectively, so pH gradient could reduce the absorption of dauricine; chelator EGTA couldn't affect the P_app, ER and accumulation transport amount of dauricine. Conclusion : The active transport was included in the absorption mechanism of dauricine,pH gradient could increase the polar phenomenon, transmembrane pathway is the main absorption route for dauricine.