在体单向肠灌流模型研究大黄素的大鼠肠吸收特性

Study of Intestinal Absorption of Emodin in One-way Intestinal Perfusion Rat Model

目的研究大黄素在大鼠不同肠段的吸收特性,以及P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP2)对大黄素肠吸收的影响。方法采用大鼠在体单向肠灌流模型,HPLC法测定肠灌流液中大黄素的浓度,计算不含抑制剂药物组及含抑制剂药物组大黄素的吸收速率常数(Ka)和表观吸收系数(Papp)。结果十二指肠段吸收能力显著强于其他肠段(P<0.05);大黄素在回肠、结肠、空肠段之间的吸收差异无统计学意义(P>0.05);加入P-gp抑制剂后,大黄素肠吸收的Ka、Papp值与不含抑制剂组比较差异也没有统计学意义(P>0.05);加入高、中浓度MRP2抑制剂后,大黄素肠吸收的Ka、Papp值与不含抑制剂组比较,差异均有统计学意义(P<0.01),且有剂量依赖性。结论大黄素在大鼠体内的主要吸收部位为十二指肠。大黄素的肠吸收过程不受P-gp的外排影响,但受到MRP2的肠道外排转运影响,大黄素可能为MRP2的底物。

Objective To investigate the absorption characteristic of emodin in rats intestine and to observe the impact of P-glycoprotein（P-gp） and multidrug resistance-associated protein（MRP2） on intestinal absorption of emodin. Methods The rat one-way intestinal perfusion model was used. The concentration of emodin was determined by RP- HPLC. The absorption rate constant（Ko） and the apparent absorption coefficient（Papp） in each intestinal section were calculated in rats with or without P-gp inhibitor（verapamil hydroehloride） or MRP2 inhibitor（ indomethacin ）. Re- sults The value of Ka and Papp in the duodenum was signifcantly higher than in other intestinal sections（P 〈 0.05 ）, and the absorption of emodin had no signifcant difference among inileum,colon and jejunum（P 〉 0.05）. Compared with the group without inhibitor, the value of Ka and Papp had signifcantly increased（P 〈 0.01 ） affter addinge high- and moderate- concentration inhibitor of MRP2, and the increase of the value was in dose-dependent manner. How- ever, the intestinal absorption of emodin had no significant difference（P 〉 0.05） affter adding the inhibitor of P-gp. Conclusion The main absorption position of emodin is in the duodenum of rats. P-gp has no effect on the intestinal absorption of emodin, but MRP2 can promote the intestinal absorption of emodin. Emodin may be the substration of MRP2.