单向在体肠灌流模型研究P-gp和MRP2抑制剂对芒果苷肠吸收的影响  

Effects of P-gp and MRP2 inhibitor on intestinal absorption of mangiferin in rats by in-situ single-pass perfusion model

作　　者：何倩梅[1] 李丹[1] 邱昆成 孙振刚[1] 刘奕明[1] 

机构地区：[1]广州中医药大学附属广东省中医院,广州510120

出　　处：《中药药理与临床》2016年第4期35-38,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：广东省中医院中医药科学技术研究专项资助(No.YN2014ZHR206);广东省科技厅科技计划项目(No.2014A020221115)

摘　　要：目的:研究P糖蛋白(P-gp)和多耐药相关蛋白2(MRP2)对芒果苷肠吸收的影响。方法:采用大鼠单向在体肠灌流模型,以酚红为标示物;UPLC法测定灌流液中芒果苷的含量,计算芒果苷在空肠和回肠段及加入P-gp抑制剂和MRP2抑制剂后的吸收常数(Ka)和表观渗透系数(Peff)。结果:芒果苷(5μg/ml)在回肠和空肠的吸收差异无统计学意义。在回肠段,加入P-gp抑制剂维拉帕米(0.1mmol/L)和环孢霉素A(0.1mmol/L)或MRP2抑制剂吲哚美辛(0.04mmol/L)后,芒果苷吸收的Peff值和Ka值均明显增加;在空肠段,维拉帕米可明显升高芒果苷吸收的Ka值,而其他各组的Peff值和Ka值虽有一定程度的增加,但无显著性差异。结论:P-gp和MRP2抑制剂对芒果苷的肠吸收,特别是回肠吸收,具有明显的促进作用,提示芒果苷为P-gp和MRP2的底物。Objective： The purpose of this study is to investigate the influence of P-glycoprotein （P-gp） and multidrug resistance-associated protein 2 （MRP2） on the intestinal absorption of mangiferin. Methods. The intestinal absorption studies of manglferln were examined by in-situ sin- gle pass perfusion models in rats and UPLC. Phenol red was used as a marker substance. The absorption rate constant （Ka） and the apparent absorption coefficient （Peff） of mangiferin in the ileum and jejunum with or without P-gp inhibitor or MRP2 inhibitor were calculated by the determined mangiferin concentration. Results： There was no significant statistical difference between the absorption of mangiferin （StLg/ml） in the ileum and jejunum （ P 〉 0.05）. The Peff and Ka values of mangiferin in the ileum were significantly increased in the P-gp inhibitor （Verapamil （0. lmmol/L） and cyclosporin A （0. 1mmol/L）） group and MRP2 inhibitor （indomethacin（0.04mmol/L）） group, which sta- tistically differ from those of the mangiferin group （ P 〈 0.05 or P 〈 0.01 ）. In addition , the Ka value of P-gp inhibitor （verapamil） group inthe jejunum was significantly increased in comparison to the mangiferin group （ P 〈 0.05 ）, while the Peff and Ka values of mangiferin were slightly increased in the P-gp inhibitor （cydosporin A） and MRP2 inhibitor （indomethacin） groups （P 〉 0.05）. Conclusion： Both P-gp and MRP2 inhibitor can improve the absorption of mangiferin in the ileum and jejunum, especially in ileum, which suggesting that mangiferin may be the substrate of P-gp and MRP2.

关 键 词：芒果苷 P-糖蛋白 MRP2 单向在体肠灌流 

分 类 号：R285.5[医药卫生—中药学]