马钱子碱体外吸收机制及其与甘草苷的转运相互作用研究

Study on the absorption mechanism of brucine in vitro and its transport interaction with liquiritin in Caco-2 cell monolayer model

目的:研究马钱子碱在Caco-2单层细胞模型中的吸收与转运情况,以及与甘草苷合用对马钱子碱吸收与转运的影响。方法:以Caco-2单层细胞为体外研究模型,考察转运时间、药物作用浓度、P-糖蛋白抑制剂维拉帕米、介质pH值对马钱子碱单用及与甘草苷合用时,马钱子碱的累积吸收浓度(TRcum)和表观渗透系数(Papp)的影响。结果:马钱子碱单用时,其Papp值均>10-6cm/s,PappB→A/PappA→B均<1.5。马钱子碱与甘草苷合用,明显升高了PappB→A/PappA→B值;马钱子碱与维拉帕米合用,显著降低了PappB→A/PappA→B值。介质pH6.0时的PappA→B值显著<介质pH7.4时PappA→B值。结论:马钱子碱以被动转运为主,P-gp及甘草苷对其吸收有明显抑制作用,介质pH值对其吸收也有重要影响。

Objective： To study the absorption mechanism of brucine in vitro and its transport interaction with liquiritin in Caco-2 cell monolayer model.Methods： The cumulative transport concentration（TRcum）,apparent permeability coefficient（PappB→A and PappA→B） of brucine were determined after Caco-2 cell monolayer model were treated by brucine and combined with liquiritin.The effects of drug concentration,conveying time,P-glycoprotein inhibitor verapamil and medium pH value on the transport of brucine in Caco-2 cell monolayer model were also investigated.Results： The Papp value of brucine was larger than 10-6cm/s,and the ratio of Papp B→A versus Papp A→B was less than 1.5.The co-treatment of brucine combined with liquiritin increase the ratio of Papp B→A versus Papp A→B,whereas the co-treatment of brucine combined with verapamil decreased the ratio of Papp B→A versus Papp A→B.Moreover,the Papp A→B in medium pH6.0 was less than that in medium pH7.4.Conclusion： The absorption of brucine in Caco-2 cell monolayer model was well and the passive transference was its main intestinal absorption mechanism.P-glycoprotein and liquiritin inhibited the absorption of brucine,and medium pH had important effect on the transport of brucine.