树豆酮酸A在Caco-2细胞单层模型的转运机制研究

Transport Characteristics of Cajanonic Acid A across Caco-2 Cell Monolayer Model

目的通过建立体外Caco-2细胞模型研究树豆酮酸A的吸收特性。方法通过MTS实验考察树豆酮酸A不同浓度对Caco-2细胞的毒性,考察树豆酮酸A从AP→BL和BL→AP的双向转运,计算累计转运量以及表观渗透系数(P_(app)),进一步探究转运量与其浓度、时间、以及P-糖蛋白抑制剂维拉帕米的关系。结果树豆酮酸A的转运量呈剂量和时间依赖性增加,AP→BL树豆酮酸A P_(app)值为2.01×10^(-6)～3.95×10^(-6)cm·s^(-1),BL→AP树豆酮酸A P app值为2.51×10^(-6)～6.03×10^(-6)cm·s^(-1),外排率ER接近1.5。结论提示树豆酮酸A在Caco-2细胞模型上的吸收不是简单的被动扩散,其外排比提示可能含有外排蛋白P-糖蛋白的参与,表观渗透系数推测其口服吸收为中等吸收。

OBJECTIVE To study the absorption characteristics of cajanonic acid A using in vitro Caco-2 cell model. METH-ODS The toxicity of cajanonic acid A on Caco-2 cells was investigated by MTS, the bi-directional transport of cajanonic acid A from A→BL and BL→AP was investigated, the cumulative transport and apparent permeability （Papp） were calculated, and the relation-ships between the transport amount and concentration, time, and the P-glycoprotein inhibitor verapamil were further studied. RE-SULTS The transport amount of cajanonic acid A increased with time and concentration, the Papp from apical（AF） side to basolateral （BL） side was 2. 01 × 10^（-6）-3.95 × 10^（-6） cm · s-1, and the Papp from basolateral（BL） side to apical（AP） side was 2. 51 × 10^（-6）-6. 03 × 10^（-6） cm · s-1 CONCLUSION The current data suggests that the absorption of cajanonic acid A in the Caco-2 cell model is not a simple passive diffusion, the efflux ratio indicates that the efflux protein of P-gp may be involved, and the Papp suggests that the oral absorption is medium.