药物转运蛋白对灯盏花素小肠吸收的影响

Effects of drug transporters on intestinal absorption of breviscapine

目的:研究药物转运蛋白P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP2)对灯盏花素小肠吸收的影响。方法:HPLC法测定大鼠肠液中灯盏花素的浓度,以大鼠在体单向灌流实验(SPIP)研究药物的小肠吸收,计算不含抑制剂药物组和含抑制剂药物组的小肠表观渗透系数(Papp)。结果:含P-gp抑制剂药物组与原药组相比,Papp没有显著变化;含MRP2抑制剂药物组与原药组相比,Papp显著增加。结论:P-gp对灯盏花素的小肠吸收基本没有影响,而MRP2可将吸收的灯盏花素从肠上皮细胞内又转运回肠腔,从而降低灯盏花素的吸收。

Aim： To investigate the effects of drug transporters, including P-glycoprotein （P-gp）and multidrug resistance-associated protein（MRP2）, on intestinal absorption of breviscapine. Methods： Breviscapine concentration in rat intestinal perfusion solution was determined by HPLC. Rat single pass intestinal perfusion（SPIP）was employed to study breviscapine intestinal absorption in order to evaluate the intestinal apparent permeation coefficients （Papp） of breviscapine group and inhibitor group. Results： Based on the statistical analysis of Papp, P-gp inhibitor has no marked effects on the intestinal absorption of breviscapine. While for MRP2 inhibitor, Papp were significantly higher than that of the breviscapine group. Conclusion： P-gp transporter has no effect on intestinal absorption of breviscapine, and MRP2 transporter is involved in the intestinal absorption of breviscapine possibly via transporting breviscapine from intestinal epithelium to intestinal cavity.