CAJ | 학술논문

目的：利用Caco-2细胞模型研究8-异丙胺亚甲基橙皮素(IPHP)在小肠吸收转运的机制。方法在Caco-2细胞模型上进行IPHP的跨膜转运实验,探讨药物浓度、pH、温度、P-gp抑制剂维拉帕米、MRP2抑制剂MK-571和丙磺舒对IPHP在体外细胞模型上跨膜转运的影响。结果IPHP在Caco-2细胞模型上的转运具有一定的浓度依赖性, IPHP不同浓度从A侧到B侧的渗透系数Papp(AP-BL)(×10-5)分别为：(2．21±0．200)、(3．56±0．306)、(3．81±0．179)、(4．23±0．229)、(4．17±0．262)cm·s-1, B侧到A侧的渗透系数Papp(BL-AP)(×10-5)分别为：(3．57±0．209)、(4．51±0．113)、(4．97±0．229)、(5．24±0．550)、(5．07±0．557)cm·s-1,外排率分别为：1．61、1．26、1．3、1．23、1．21。温度和pH对其转运均有影响,而P-gp抑制剂对于IPHP的转运没有明显的影响, MRP2抑制剂在一定程度上增加了IPHP的转运量(P<0．05)。结论IPHP在Caco-2细胞模型上的转运方式主要是被动扩散,且其转运不受P-gp外排
목적：이용Caco-2세포모형연구8-이병알아갑기등피소(IPHP)재소장흡수전운적궤제。방법재Caco-2세포모형상진행IPHP적과막전운실험,탐토약물농도、pH、온도、P-gp억제제유랍파미、MRP2억제제MK-571화병광서대IPHP재체외세포모형상과막전운적영향。결과IPHP재Caco-2세포모형상적전운구유일정적농도의뢰성, IPHP불동농도종A측도B측적삼투계수Papp(AP-BL)(×10-5)분별위：(2．21±0．200)、(3．56±0．306)、(3．81±0．179)、(4．23±0．229)、(4．17±0．262)cm·s-1, B측도A측적삼투계수Papp(BL-AP)(×10-5)분별위：(3．57±0．209)、(4．51±0．113)、(4．97±0．229)、(5．24±0．550)、(5．07±0．557)cm·s-1,외배솔분별위：1．61、1．26、1．3、1．23、1．21。온도화pH대기전운균유영향,이P-gp억제제대우IPHP적전운몰유명현적영향, MRP2억제제재일정정도상증가료IPHP적전운량(P<0．05)。결론IPHP재Caco-2세포모형상적전운방식주요시피동확산,차기전운불수P-gp외배
Aim To study the mechanism of 8-isopro-pylaminomethyl hesperitin ( IPHP ) intestinal absorp-tion using Caco-2 cell lines. Methods Using Caco-2 cell lines as an intestinal epithelial cell model, the effects of drug concentration, temperature, pH, P-gly-coprotein ( P-gp) inhibitor verapamil and multidrug re-sistance protein 2 ( MRP2 ) inhibitors MK-571 or pro-benecid on IPHP transport across Caco-2 cell lines were all investigated. Results The transportation of IPHP was related to drug concentration. The Papp ( AP-BL) ( × 10 -5) was (2. 21 ± 0. 200) cm·s-1,(3. 56 ± 0. 306) cm·s-1,(3. 81 ± 0. 179) cm·s-1,(4. 23 ± 0. 229 ) cm · s-1 , ( 4. 17 ± 0. 262 ) cm · s-1 , re-spectively, and Papp(BL-AP) ( × 10 -5) was (3. 57 ±0. 209) cm·s-1,(4. 51 ± 0. 113) cm·s-1,(4. 97 ± 0. 229) cm·s-1,(5. 24 ± 0. 550) cm·s-1,(5. 07 ± 0. 557) cm·s-1,respectively. Efflux rate was 1. 61, 1. 26,1. 3,1. 23,1. 21,respectively. Temperature and pH both influenced the transport, While the P-gp in-hibitor verapamil had no effect on the transport of IPHP. MRP2 inhibitors MK-571 or probenecid led to an apparent decrease in the efflux of IPHP. Conclu-sion The results suggest that the transport of IPHP is mainly passive diffusion, and MRP2 but not P-gp may be involved in the transport of IPHP.