中药成分对大鼠cyp3a4酶代谢影响的研究 - 中国实验动物学报.doc

四种中药成分对大鼠CYP2A6酶代谢影响的研究 mol/L、代谢时间1.5h、PH值7.0、孵育温度37℃。Research External Condition and Monomeric Chinese Medicine Concerning the Effect on the Rat CYP2A6 Enzyme Metabolism LIU Jie1, GENG Xiang-fei2, REN Juan3 (1.General Hospital of PLA Second Artillery, Beijing 100088, China; 2. Beijing LAT Science Co., Ltd., Beijing 100094, China) 【Abstract】 Objective To take coumarin medicine as a tool. To explore the metabolic conditions of liver microsomes in vitro and the interaction between the coumarin and monomeric Chinese medicine. Method We studied the best metabolic conditions of liver microsomes in vitro in the following four aspects: substrate concentration, metabolism time, PH value and incubation temperature. furthermore, we studied the interactions between the coumarin and four monomeric Chinese medicine. (as following: Tetrahydropalmatine, Sinomenine hydrochloride, Neferine and Panax notoginseng saponins ).Results The best metabolic conditions of Liver microsomes in vitro including four aspects as like: substrate concentration was 100μmol/L, 1.5 hours of Metabolism time, PH value of 7.0, Incubation temperature of 37℃.In terms of the interaction, ------------------ 【作者简介】刘洁（1983--），女，临床医师，研究方向：临床医学。 【通讯作者】任娟。E-mail：lat186@163.com。 Tetrahydropalmatine, Sinomenine hydrochloride, Neferine and Panax notoginseng saponins had a Inhibitive impact on the metabolism with varying degrees. Conclusions Taking the drugs through metabolism of CYP2A6 enzyme as a reference, the results gave some mirror to the safety of clinical medication. 【Key words】 Coumarin； Liver microsomes； Interaction 细胞色素P450（cytochrome P450，CYP）超基因家族是人体内最重要的药物代谢酶，其中的一些亚型所具有的基因多态性表现出人体对药物和/或环境化合物毒性、敏感性存在差异，CYP2A6为其一例[1]。CYP2A6是CYP2A亚家族重要成员之一,约占整个P450酶系统的5%,对很多药物和环境中化合物的清除起重要作用,参与许多药物代谢,还可激活许多结构上非相关的前致癌物[2],比如它能将许多致癌原如黄曲酶毒素B1、烟草中大量的亚硝胺致癌原激活为强致癌物，N-亚硝基二甲胺激活为强致癌物则与肺癌罹患率显著相关[34]。香豆素是CYP2A6特异性的底物，能被CYP2A6代谢为7-OH香豆素排出体外[2]。因为大鼠本身不存在CYP2A6，只有类似功能的代谢酶CYP2A5[5]，只有通过苯巴比妥钠诱导大鼠才能产生CYP2A6[6]。本实验基于此通过大鼠诱导的肝微粒体以香豆