在体单向灌流法研究Rho-123大鼠肠吸收特性  

Intestinal Absorption Features of Rho-123 using in situ Single-pass Perfusion in Rats

作　　者：周国梁[1,2] 汤琦琦 俞浩[1,2] 张孝林 郭新怡[1] 单婷婷 ZHOU Guoliang;TANG Qiqi;YU Hao;ZHANG Xiaolin;GUO Xinyi;SHAN Tingting(Anhui Science and Technology University, Bengbu 233100 Anhui, China;Anhui University of Chinese Medicine, Hefei 230012 Anhui, China)

机构地区：[1]安徽科技学院,安徽蚌埠233100 [2]安徽中医药大学,安徽合肥230012

出　　处：《中药新药与临床药理》2018年第3期347-352,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：安徽省高校省级自然科学研究重点项目(KJ2014A051);安徽省教育厅重点和重大项目(KJ2016SD16);2017年安徽省大学生创新创业训练计划项目(2017S10879006)

摘　　要：目的研究罗丹明123(Rho-123)在大鼠体内肠吸收特性,并分析P-糖蛋白(P-gp)和多药耐药相关蛋白2(MRP2)对Rho-123吸收影响关系。方法采用HPLC法建立大鼠Rho-123肠灌流液分析方法,根据所建立的分析方法对大鼠在体肠吸收影响因素进行考察。以吸收速率常数(Ka)和表观渗透系数(Papp)分析参数为指标,确定大鼠在体肠单向灌流条件,并进一步分析P-gp抑制剂和MRP2抑制剂对Rho-123肠道吸收影响关系。结果研究Rho-123在大鼠肠道药物吸收条件为:选择在空肠段进行灌流、灌流质量浓度为40 ng·m L^(-1),灌流体积流量为0.2 m L·min^(-1),肠道分析长度为10 cm,灌流初始平衡30 min后,恒速灌流105 min,P-gp抑制剂盐酸维拉帕米对Rho-123在大鼠体内肠吸收有影响,MRP2抑制剂吲哚美辛对Rho-123在大鼠肠道吸收无影响。结论 Rho-123可以作为研究P-gp肠道药物吸收特性的底物,方法可靠性好。Objective Rho-123 absorption characteristics of various intestinal segments was studied in living rats,and the influence of P-glycoprotein（P-gp）and multi-resistant related protein 2（MRP2）on absorption of Rho-123 was analysed. Methods High Performance Liquid Chromatography（HPLC）method was established to analyse Rho-123 in rat intestinal perfusion. Using Kaand Pappas indexes,parameters of single-pass perfusion in live rats’ intestine was optimized and influence of P-gp inhibitors and MRP2 inhibitors on Rho-123 absorption was determined. Results The condition of single-pass perfusion in intestine of living rats are as follows：using perfusion concentration of 40 ng·m L^-1,a perfusion volume flow of 0.2 m L·min^-1 in 10 cm intestine,with a equilibrium time of 30 min,and then perfuse for 105 min. Results The P-gp inhibitor（verapamil hydrochloride）had an effect on Rho-123 absorption in rat intestine,and no influence was observed for MRP2 inhibitors（indomethacin）. Conclusion Rho-123 can be used as a P-gp intestinal substrate in the intestinal drug absorption. The reliability of the established method is good in this study.

关 键 词：单向灌流法 罗丹明123 肠内吸收特征 

分 类 号：R285.5[医药卫生—中药学]