转细胞色素P450酶人源化小鼠及应用的研究进展  

Progress in cytochrome P450 humanized mice and its applications

作　　者：程一帆 马璟 严东明 

机构地区：[1]中国医药工业研究总院国家上海新药安全评价研究中心,上海201203

出　　处：《中国药理学与毒理学杂志》2013年第6期1033-1037,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家科技重大专项(2012ZX09505001-003)~~

摘　　要：细胞色素P450酶系(CYP)参与了超过75%的药物和多种内源性化学性物质和前致癌物的Ⅰ相代谢反应,有重要的临床意义和科研价值。传统的体外模型能够检测P450酶的基本功能,但不能够体现其在生物体内的实际情况。由于CYP复杂的遗传多态性,普通的动物模型实验数据外推至人有着极大的不确定性。构建转CYP人源化小鼠模型可以解决上述问题。目前主要有转人CYP1A,CYP2D6,CYP3A,CYP4F2和PXR/CYP3A4人源化小鼠等类型的小鼠模型。运用人源化小鼠模型进行药代动力学及毒理学的研究,有助于获得更可靠的体内实验数据并较准确预测外源化合物在人体内的代谢情况。这些人源化小鼠模型在评估和预测药物毒性风险和促进安全用药等方面有广泛的应用。本文综述了转细胞色素P450酶人源化小鼠及应用的研究进展。The cytochrome P450 enzymes （CYP） are responsible for more than 75% of phaseⅠ dependent drug metabolism and for the metabolism of a huge variety of endogenous chemicals and precarcinogens. They are of great importance for clinical significance and scientific value as the major metabolic enzymes. In vitro traditional models can detect the basic functions of CYP enzymes but hardly to reflect the actual situation in vivo. Moreover, ordinary animal models＇ test data extrapolation in human causes a great deal of uncertainty due to the complex genetic polymorphism of CYP. Generated humanized mouse models which can express human＇s CYP will solve the above problems. Nowadays, the types of humanized mouse contain CYP1A subfamily, CYP2D6, CYP3A subfamily, PXR/CYP3A4, CYP4F2 and so forth. Humanized mouse models are used for pharmacokinetic and toxicology studies, obtaining a more reliable in vivo test data and predicting the real metabolism of exogenous compounds in vivo. These humanized mouse models will have widely use in the assessment and prediction of drug toxicity risk and promote safer drugs and so on. The paper summarized the progress in cytochrome P450 humanized mice and its applications.

关 键 词：小鼠 转基因 药代动力学 毒理遗传学 细胞色素P450酶系统 

分 类 号：R965.1[医药卫生—药理学]