金丝桃苷在Caco-2细胞模型中的跨膜转运方式

目的研究金丝桃苷在Caco-2细胞模型中的吸收机制。方法用Caco-2细胞单层模型研究金丝桃苷的双向转运,考察pn、药物质量浓度、方向、温度、抑制剂对金丝桃苷细胞转运的影响。采用HPLC法检测金丝桃苷的含量,计算其表观渗透系数(P_app)。结果金丝桃苷的细胞转运P_app。具有pH依赖性。金丝桃苷肠腔（A）侧→基底（B）侧P_app>B→A,并且随着金丝桃苷质量浓度的增大而减小,具有浓度依赖性。P-gp抑制剂维拉帕米增加金丝桃苷的细胞正向转运P_app,降低了其逆向转运P_app。金丝桃苷较高浓度时,MRPl抑制剂吲哚美辛和ATP抑制剂叠氮化钠显著降低了金丝桃苷的转运量。结论金丝桃苷在Caco-2细胞单层模型中的转运具有pH依赖性和浓度依赖性,是以主动转运为主,被动扩散为辅,同时涉及外排蛋白作用的转运方式。

Absorption mechanism of hyperoside across Caco-2 cells model

AIM To research the absorption mechanism of hyperoside across Caco-2 ceils model. METHODS Depending on Caco-2 cell monolayers drug transport model to study the double transport mechanism of hyperoside, the ef- fect on hyperoside absorption of pH, drug concentration, direction, temperature and inhibitors was explored. The determi- nation of hyperoside was performed by HPLC. RESULTS The absorptive transport of hyperoside in the Caco-2 cells was pH dependence. P,pp of Apical to Basolateral was much more than that of Basolateral to Apical, and reduced by the con- centration increasing of hyperoside,so it was also concentration dependence. P-~ inhibitor verapamil enhanced the ab- sorptive transport of hyperoside from Apical to Basolateral,and reduced the absorptive transport of hyperoside from Baso- lateral tO Apical. On the high concentration of hyperoside, MRP1 inhibitor indomethacin and ATP inhibitor sodiumazide significantly reduced the absorptive transport of hypereside. CONCLUSION The absorption transport of hyperoside is pH and concentration dependence, absorption of hyperoside in Caco-2 cell model should be an active transport primarily supplemented by passive diffusion,along with excretion mediated action. The ability of active transport is much more than that of passive diffusion.