千金子甾醇在Caco-2细胞单层模型中的吸收研究

Absorption of euphobiasteroid across Caco-2 cell monolayer model

目的 研究千金子甾醇在Caco-2细胞单层模型中的吸收和转运.方法 用Caco-2细胞模型研究千金子甾醇在Caco-2细胞模型中的双向转运,考察时间、药物浓度和P-糖蛋白抑制剂对千金子甾醇跨膜转运的影响.采用UPLC-MS/MS法测定药物浓度,计算表观渗透系数（Papp）以及表观渗透率（PDR）.结果 在Caco-2细胞中的转运过程中,不同浓度千金子甾醇的Papp值介于1×10-6^-1×10^-5,其累积转运量随时间和浓度的增加而增加,具有浓度依赖性.10、30、50 μmol/L千金子甾醇的PDR分别为1.35、0.83、0.65.盐酸维拉帕米可以促进千金子甾醇由AP侧→BL侧的转运.结论 千金子甾醇在肠道中的吸收中等,以被动转运为主,可能存在肠道转运蛋白的外排机制.

Objective To study the absorption and transportation ofeuphobiasteroid in Caco-2 cell monolayer model. Methods Caco-2 cell monolayer model was used to study the process of bi-direction transport of euphobiasteroid, and the effects of time, drug concentration, and inhibitors on the process were investigated. The concentration of euphobiasteroid was detected by UPLC-MS/MS, and the apparent permeability coefficient （Papp） and apparent permeability （PDR） were calculated. Results During the transport process of euphobiasteroid in Caco-2 cells, the Papp values of variety concentration were from 1 × 10^-6 to 1 × 10^-5. The cumulative transshipment volume was increased with time and concentration, which presented concentration-dependent manner. The PDR values of 10, 30, and 50 grnol/L euphobiasteroid were 1.35, 0.83, and 0.65, respectively. Verapamil hydrochloride could promote the transportation of euphobiasteroid from AP side to BL side. Conclusion The absorption of euphobiasteroid in intestine is moderate and mainly through passive transport. There may be excretion mechanism of intestinal transport protein in the intestine absorption of euphobiasteroid.