目的研究熊果酸在Caco-2细胞单层模型中的吸收转运机制。方法利用人源结肠腺癌细胞系Caco-2细胞单层模型研究熊果酸在有或无P-糖蛋白专属性抑制维拉帕米存在时,评价其双向转运特征,并考察时间、药物浓度、体系温度以及培养介质pH值对Caco-2细胞摄取熊果酸的影响。采用高效液相色谱-紫外检测法对熊果酸进行定量分析,计算其表现渗透系数(P_app)。结果浓度在10～40μmol/L内,Caco-2细胞对熊果酸摄取量呈线性增加。双向转运研究发现加入P-糖蛋白专属性抑制剂维拉帕米后,其P_app发生显著改变,表观渗透率由3.445下降至1.386。结论熊果酸在Caco-2细胞模型的吸收转运机制以被动转运为主,P-糖蛋白参与主动转运的过程。

Objective To study the absorption and transport mechanism of ursolic acid(UA) by using Caco-2 monolayer model.Methods Evaluating the transport characteristic through studying whether P-glycoprotein(P-gp) transporter inhibitor Verapamil(VER) exists or not by using Caco-2 cell monolayer as an intestinal epithelial cell model and investigating the effects of uptake time,drug concentration,system temperature,and pH value of culture media on the uptake of UA.The drug concentration was measured by HPLC coupled with UV detector.Transport parameters and apparent permeability coefficients (P_(app)) were then calculated.Results In the concentration range of 10-40μmol/L,the uptake of UA by Caco-2 cell all linearly increased.The P_(app) of UA transported on Caco-2 cell monolayer model significantly changed when the specificity inhibitory of P-gp was added to model and the apparent permeability ratio decreased from 3.445 to 1.386.Conclusion The intestinal absorption of UA is passive diffusion as the dominating process and active transportation mediated by P-gp transporter in Caco-2 cell monolayer model.