Caco-2细胞模型考察不同转运蛋白对瑞香素口服吸收的影响

目的:研究在Caco-2细胞模型中不同转运蛋白对瑞香素吸收的影响。方法:采用Caco-2细胞单层模型研究转运蛋白对瑞香素的吸收影响。采用HPLC法检测药物浓度,计算其表观渗透系数,考察不同转运蛋白抑制剂对瑞香素吸收的影响。结果:在10μg/ml的瑞香素溶液中加入P-gp抑制剂维拉帕米50μmol后,瑞香素PBA/PAB均无显著性差异(P>0.05);加入MRP2抑制剂环孢素10μmol后,PBA/PAB降低了10%;加入BCRP抑制剂潘生丁25μmol后,PBA/PAB降低了29%。结论:在瑞香素的跨膜转运的过程中不存在肠道转运蛋白P-gp的作用,但可能存在MRP2、BCRP的外排。

The influences of different transporters on the oral administration of daphnetin in Caco-2 monolayer cell model

Objective: Study the influences of different transporters on the absorption of daphnetin in Caco-2 monolayer model.Method: The influences of transporters on the absorption of daphnetin were study in Caco-2 monolayer model.The compound was determined by high-performance liquid chromatography.The apparent permeability coeffients(Papp) was calculated to study the influences of different transporters on the absorption of daphnetin.Result: Add the inhibitors of MRP2 cyclosporine 10μmol and the inhibitors of BCRP dipyridamole 25μmol to the solution of daphentin(10μg/ml) can reduce the ration of Papp of daphnetin by 10% and 29%,respectively.While the inhibitors of P-gp verapamil 50μmol have no significant effects on Papp values(P>0.05).Conclusion: The absorption of daphnetin was passive diffusion at the dominating process.Daphnetin may be a substrate of BCRP and MRP2,but not P-gp substrate.