丹参脂溶性成分在Caco-2细胞模型中吸收机制研究

 目的研究丹参脂溶性成分在Caco-2细胞模型中的吸收机制。方法以Caco-2细胞作为吸收研究模型,分别测定了各种条件下,包括分别以单体丹参酮Ⅱ_A和丹参醇提取物给药、改变给药浓度、改变转运方向以及加入影响吸收的物质,丹参酮Ⅱ_A,隐丹参酮和丹参酮Ⅰ的转运情况。结果给予不同剂量的丹参酮ⅡA,其表观通透系数P_app随浓度的增加先降低后升高; 丹参酮Ⅱ_A细胞绒毛侧Apical→基底侧Basolateral转运(AP→BL)大于BL→AP 5倍以上;随着冰片含量增加,丹参脂溶性成分的 P_app明显增大;EDTA对吸收没有明显影响。结论丹参酮Ⅱ_A在Caco-2细胞模型中的转运机制类似载体介导转运兼有被动扩散,无细胞旁路途径,无外排泵参与;冰片有促吸收的作用。本实验结果为含丹参的制剂研究、口服给药等提供信息。

Absorption Mechanism of Liposoluble Components of Salvia miltiorrhiza with Caco-2 Cell Model

OBJECTIVE To study the absorption mechanism of liposoluble components of Salvia miltiorrhiza with Caco-2 cell model . METHODS Caco-2 cell was used an drug absorption model. The transportation of tanshinon Ⅱ_A, cryptotanshinone and tanshinone Ⅰ across Caco-2 cell were determined under various conditions, including giving tanshinone Ⅱ_A and the ethanol extract of Salvia miltiorrhiza respectively, changing dosage and transport direction, adding some appropriate substances affecting absorption.RESULTS With the increasing of tanshinone Ⅱ_A concentration, the apparent permeability coefficient (P_app) decresed at first then increased. The P_app of transport from AP to BL was five times more than that from BL to AP. With increasing dosages of borneol, the P_app increased obviously. Drug transport was not affected by EDTA. CONCLUSION The transport mechanism of tanshinon Ⅱ_A in vivo is rather complex and involves carrier-mediated transport and passive transcellular diffusion, with neither paracellular route nor P-gp efflux. Borneol can promote transport ofliposoluble components across Caco-2 cell.The present study provided useful information for formulation study, oral administration and etc.