小檗碱在Caco-2细胞单层模型中吸收和外排机制的研究

Mechanism of absorption and efflux of berberine in Caco-2 cell monolayer

目的利用Caco-2细胞单层模型研究小檗碱的双向转运和外排动力学机制。方法超高液相色谱法测定Tran-swell^TM中供给池和接受池中小檗碱的浓度，计算其表观渗透系数（Papp），分析P-糖蛋白外排泵（P-gP）的作用。结果不同浓度小檗碱由肠腔面到基底面（A→B面）的Papp约在（2-3）×10^-6，吸收量与浓度成线性关系，而由基底面到肠腔面（B→A面）的Papp约在（2-3）X10^-5，约是A—B面的8～10倍，给予P→gP抑制剂维拉帕米后B→A面的外排转运明显减低，A→B面的吸收明显增加。结论小檗碱是以被动扩散为主要转运方式被小肠上皮细胞摄取和转运，属吸收中等的药物，且存在P-糖蛋白介导的外排机制。

AIM To study the mechanism of bi-direction transport and efflux of berberine by using Caco-2 monolayer model. METHODS The concentration of berberine in the apical side （ AP side） and basolateral side （ BL side） was determined by UPLC, and their apparent permerability coefficient （Papp） was calculated, the ef flux P-glycoprotein of berberine was analyzed. RESULTS The apparent permeability coefficient of AP side to BP side under the condition of different berberine concentrations was about （2 -3） × 10^-6 and presented absorption and-concentration linear relationship. The apparent permeability coefficient of BP side to AP side was about （2 - 3 ） x 10^ - 5 Ratios of Papp（ BL-AP） and Papp（ AP-BL） ranged from 8 tol0. The efflux transport of BP side to AP side decreased with the P-glycoprotein inhibitor verapamil, the efflux transport of AP side to BP side was the contrary. CONCLUSION The intestinal epithelial cells transport of berberine may be passive diffusion and P-glycoprotein plays an important role in the efflux of berberine.