【摘要】 目的 采用人结肠癌上皮细胞单层模型（Caco-2 细胞模型）研究芒果苷在小肠吸收转运的特性，探讨芒果苷的口服吸收机制。方法 采用 Caco-2 细胞模型进行芒果苷的跨膜转运实验，探讨时间、pH 值、浓度、外排转运蛋白 P-糖蛋白（P-gp）抑制剂、多药耐药相关蛋白 2（MRP2）抑制剂、乳腺癌耐药蛋白（BCRP）抑制剂对芒果苷转运的影响。结果 芒果苷在 Caco-2 细胞模型上的转运具有时间依赖性，不同浓度芒果苷在 Caco-2 细胞的表观渗透系数(P_app)无显著性差异，微绒毛面顶侧（AP）到底侧（BL）的 P_{app（AP→BL）}为（8.33±1.99）×10^-6～（8.48±1.15）×10^-6cm·s^-1,BL 侧到 AP 侧的 P_{app（BL→AP）}为（29.19±3.64）×10^-6～（33.20±5.72）×10^-6cm·s^-1,P_{app（BL→AP）}明显大于P_{app（AP→BL）}（P<0.05），药物外排率（ER）大于 3；芒果苷的 P_app随 pH 的增加而显著性增加；P-gp 抑制剂维拉帕米（P<0.001）和环孢素 A（P<0.05）能显著增加芒果苷 AP→BL 方向的表观渗透系数；MRP2 抑制剂 MK571 显著减少芒果苷两侧表观渗透系数（P<0.01）;BCRP 抑制剂白杨素和烟曲霉素 C 对芒果苷的转运无明显影响。结论 芒果苷为中等吸收药物，碱性环境有利于其转运，在 Caco-2 细胞模型上的转运方式以被动扩散为主，并存在主动转运，不受外排蛋白 BCRP 的影响，但与 P-gp 有关，MK571 与芒果苷可能存在竞争转运。更多还原

【Abstract】 Objective To investigate the transport characteristics of mangiferin in Caco-2 cell model and to clarify the oral absorption mechanism of mangiferin. Methods Effects of time,pH,concentration,P-gp inhibitor,MRP2inhibitor,and BCRP inhibitor on the transportation of mangiferin in Caco-2 cell model were investigated. Results The transport of mangiferin in Caco-2 cell model was time dependent but P_appof mangiferin showed no difference in concentration,P_{app（AP→BL）}was（8.33±1.99）×10^-6cm·s^-1to（8.48±1.15）×10^-6cm·s^-1and P_{app（BL→AP）}was（29.19±3.64）×10^-6cm·s^-1to（33.20±5.72）×10^-6cm·s^-1;P_{app（BL→AP）}was significant higher than P_{app（AP→BL）}（P<0.05）and ER was more than 3. The P_appof mangiferin increased significantly with the increase of pH. P-gp inhibitors,verapamil（P<0.001）and cyclosporine A（P<0.05） obviously increased the P_{app（AP→BL）}of mangiferin. MRP2 inhibitor MK571 decreased bidirectional P_appof mangiferin markedly（P<0.01）. BCRP inhibitor chrysin and Fumitremorgin C had no effect on P_appof mangiferin. Conclusion Mangiferin was well absorbed and alkaline environment was favorable for its transport. Passive diffusion was the main absorption mechanism of mangiferin and a cellular efflux system was participated. P- gp would influence the transport of mangiferin while BCRP not MK571 and mangiferin may have competitive translocation.更多还原