丹参素在Caco-2细胞单层模型中的跨膜转运研究

目的:研究丹参素在Caco-2细胞模型中的跨膜转运机制。方法:通过研究丹参素在模型中的双向转运,考察时间、药物浓度及转运蛋白抑制剂对丹参素吸收的影响。用液相-质谱联用法检测药物浓度,计算其表观渗透系数。结果:表观渗透系数P_app值随时间延长而增大,到一定时间趋向饱和状态,并随丹参素浓度的增加而逐渐减小。双向转运的P_app比值即P_ratio均大于1.5。在加入P-gp转运蛋白抑制剂维拉帕米后,丹参素P_app,A-B值显著增大,而P_app,B-A值显著降低。结论:丹参素在Caco-2细胞模型中的转运可能主要是由P-gp转运蛋白介导的主动转运。

Transport mechanism of Danshensu across Caco-2 monolayer model

Objective: To study the absorption mechanism of Danshensu by using Caco-2 monolayer model .Method: Caco-2 cell monolayer model was used to study the bi-direction transport of Danshensu.An LC-MS method was developed to measure the concentration of Danshensu in cell culture medium and calculate the apparent permeability coefficients(P_app).The effects of time,drug concentration and inhibitor on the absorption of Danshensu were studied.Result: Transport of Danshensu was time and concentration dependent,and it was also effected by P-glycoprotein inhibitor.P_app increased with time increase and tended to become saturated at some point.It,however,decreased while concentration of Danshensu increased.P_ratiois larger than 1.5.Verapamil can cause significantly effect on transport of Danshensu: P(app,A-B) increased and P_app,B-A decreased.Conclusion: The absorption of Danshensu in Caco-2 cell model may be an active transportation mediated by P-glycoprotein transporter.