阳美松,赖泳
YANG Meisong,LAI Yong

• 1:大理大学药学与化学学院
• 2:大理大学药学与化学学院云南省昆虫生物医药研发重点实验室

摘要(Abstract)：

目的综述细胞色素P450(cytochrome P450,CYP450)酶抑制效应常用检测技术。方法查阅国内外近几年相关文献73篇,对CYP450酶抑制效应常用检测技术进行分析和归纳总结。结果检测CYP450酶抑制效应常用体内及体外两种模型,体内模型主要通过临床实验或动物实验联合高效液相色谱质谱联用或其他检测方法,测定给药前后CYP450酶探针底物代谢产物的变化量,反映药物对酶的抑制效应;体外模型中,常用肝微粒体与药物及相应探针底物共孵育后,检测探针代谢产物变化量初步反应药物对酶抑制效应,再利用药物处理原代或转基因细胞,通过相应检测技术测定细胞内CYP450酶相应的基因及蛋白表达量来研究药物对酶抑制机制。结论 CYP450酶抑制效应检测技术已趋于完善,为药物药代动力学和药效学研究提供了良好的保障。
Cytochrome P450(CYP450) enzymes are the main components which mediate metabolism of endogenous and exogenous compounds in the liver. The active inhibition of CYP450 enzymes could weaken the abilities of metabolism and elimination of the liver,which causes drugs and toxic substances accumulation,thus affecting drug effects or damaging the body. Therefore,the detection for the effects of drugs on the inhibition of CYP450 enzymes is the basis of pharmacokinetic and pharmacological research.This detection technology commonly used two models including in vivo and in vitro. The first model mainly involves clinical trials or animal experiments combined with a high performance liquid chromatography-mass spectrometry(HPLC-MS) technology or other detection methods,which are used to evaluate the variable quantity of probe substrate metabolites of CYP450 enzymes before and after drug treatment to reflect inhibitory effects of drugs on enzymes in vivo. For in vitro model,after liver microsomes are incubated together with drugs and corresponding probe substrates,the variable quantity of probe metabolites is detected to initially reflect inhibitory effects of drugs on enzymes. Then,primary or transgenic cells are treated with drugs in vitro,and expression levels of corresponding genes and proteins of CYP450 enzymes in cells are assayed with corresponding detection techniques to research theinhibitory mechanisms of drugs on enzymes.In order to provide references of techniques for the effects of drugs or other exogenous substances on the activity of CYP450 enzymes,the commonly used detection techniques for inhibitory effects of CYP450 enzymes are summarized in this article.

关键词(KeyWords)： 细胞色素P450;酶抑制效应;检测技术
cytochrome P450;inhibitory effect of enzyme;detection technology

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(81360511)

作者(Author): 阳美松,赖泳
YANG Meisong,LAI Yong

DOI: 10.14066/j.cnki.cn21-1349/r.2018.03.014

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