顺式-和反式-阿霍烯在Caco-2细胞模型中的体外摄取、转运和外排特性  

Characteristics of uptake, transport and efflux of Z-and E-ajoenes in Caco-2 cell monolayers in vitro

作　　者：田莉[1] 杨秀伟[1] 王莹[1] 徐嵬[1] 

机构地区：[1]北京大学药学院天然药物及仿生药物国家重点实验室,北京100083

出　　处：《药学学报》2007年第1期87-92,共6页Acta Pharmaceutica Sinica

基　　金：国家高技术研究发展计划(863计划)资助项目(2002AA2Z343C);国家自然科学基金资助项目(20272006);北京市科技计划专项资助项目(Z0004105040311).

摘　　要：研究顺式-阿霍烯(Z-Ajo)和反式-阿霍烯(E-Ajo)的肠细胞摄取、转运和外排特性。采用体外培养的人结肠Caco-2细胞单层模型评价,应用高效液相色谱法测定Z-Ajo和E-Ajo的含量。结果表明,仅能在Caco-2细胞单层的顶侧检测到Z-Ajo或E-Ajo;阿霍烯在Caco-2细胞中的代谢可被抗氧化剂维生素C、细胞色素P450药物代谢酶3A亚型抑制剂甲吡酮和ATP抑制剂叠氮化钠所抑制。Z-Ajo和E-Ajo皆不能透过Caco-2单层细胞而被迅速代谢,其代谢与CYP450药物代谢酶有关。The characteristics of uptake, transepithelial transport and efflux of Z- and E-ajoenes isolated from the bulbs of Allium sativum were studied. A human colon cell model Caco-2 cell monolayers in vitro cultured had been applied to study the characteristics of uptake, transepithelial transport and efflux of Z- and E-ajoenes. The quantitative determination of Z- and E-ajoenes was performed by highperformance liquid chromatography. Z- and E-Ajoenes can be detected only in the apical side and can be metabolized, but both compounds can not be transported from apical-to-basolateral and basolateral-to- apical directions in cultured Caco-2 cell monolayers. The metabolism of Z- and E-ajoenes in Caco-2 cell monolayers can be partially inhibited by vitamin C as an anti-oxidant, metyrapone as an inhibitor to subtype CYP3A of cytochrome P450 drug metabolism enzymes, and sodium azide as an inhibitor to ATP production. It is shown that neither Z-ajoene nor E-ajoene can pass through Caco-2 cell monolayers, and that they can be metabolized by the cells. The metabolism might be in correlation with cytochrome P450 drugs metabolism enzymes in Caco-2 cell monolayers.

关 键 词：阿霍烯 大蒜 CACO-2细胞单层 跨膜转运 

分 类 号：R915[医药卫生—微生物与生化药学]