淫羊藿苷在Caco-2细胞单层模型中的吸收机制

Absorption mechanism of icariin across Caco-2 monolayer model

目的:研究淫羊藿苷在Caco-2细胞模型中的吸收机制。方法:通过研究10,20μmol.L-1淫羊藿苷在细胞中的双向转运,考察时间、药物浓度及转运蛋白抑制剂对淫羊藿苷吸收的影响。用超高压液相法测定药物浓度,计算其表观渗透系数。结果:淫羊藿苷通过Caco-2细胞单层的转运量4 h内随时间延长呈线性增大,双向转运的渗透系数PBA/PAB大于4。在加入P-糖蛋白(P-gp)转运蛋白抑制剂维拉帕米后,淫羊藿苷PAB增大了1.2倍[(1.37±0.10)×10-6cm.s-1],PBA/PAB显著降低(由4.83下降到2.72)。而加入转运蛋白多药耐药蛋白(MRP2)的抑制剂白细胞三烯C4、乳腺癌耐药蛋白(BCRP)的底物潘生丁时,对淫羊藿苷转运影响不显著。结论:结果提示淫羊藿苷口服吸收差的原因有二:一是淫羊藿苷肠壁的渗透系数较小,二是可能存在肠道P-gp转运蛋白对淫羊藿苷的外排。

Objective： To study the absorption mechanism of icariin by using Caco-2 monolayer model. Method： Caco-2 cell monolayer model was used to study the bi-direction transport of icariin. The effects of time, drug concentration and inhibitor on the absorption of icariin were studied. The concentration of icariin in cell culture medium was measured by UPLC and the apparent permeability coefficients （ Papp ） was calculated. Result： The amount of icariin which was transported increased linearly with the time （ 1-4 hr）. The ratio of PBA/PAB Was larger than 4. Verapamil, the P-glycoprotein inhibitor, could cause significantly effect on transport of icariin, PAB increased, the ratio of PBA/PAB decreased. Conclusion： The reason for low absorption of icariin in Caco-2 cell model may be the secretion of the P-gp transporter.