孕烷X受体对CYP3A基因表达的调控作用及其在药物代谢中的意义  

Pregnane X receptor is involved in drug metabolism as a key regulator of CYP3A expression

作　　者：徐德祥[1] 魏伟[2] 

机构地区：[1]安徽医科大学毒理学系,安徽合肥230032 [2]安徽医科大学临床药理研究所,安徽合肥230032

出　　处：《中国药理学通报》2006年第6期646-650,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30371667;30572223)

摘　　要：细胞色素P450 3A(cytochrom e P4503As,CYP3As)在药物代谢过程中起重要作用,外源性化学物对肝脏CYP3A基因表达有明显的诱导作用。孕烷X受体(pregnane X recep-tor,PXR)是新发现的孤儿核受体(系统名:NR1 I2)。PXR与另一重要核受体RXR结合形成二聚体结合于CYP3A基因顺式反应元件,参与对CYP3A基因表达的调控作用。大量临床处方药物通过激活PXR而诱导CYP3A基因表达,构成了临床药物间相互作用的分子基础。Cytochrome P4503 As （CYP3 As）, me liver microsomal enzymes responsible for oxidative metabolism of numerous clinically used drugs, is known to be induced by a variety of compounds, including naturally occurring and synthetic glucocorticoids, pregnane compounds , and macrolide antibiotics. The pregnane X receptor （PXR; NR1I2 ） is an important component of the body＇s adaptive defense against xenobiotics including drugs. PXR is activated by a large number of endogenous and exogenous chemicals including steroids,antibiotics, antimycotics, bile acids, and the herbal antidepressant St. John＇s wort： PXR binds as a heterodimer with the 9-cis retinoic acid receptor （NR2B） to DNA response elements in the regulatory regions of CYP3A genes. Although PXR evolved to protect the body, its activation by a variety of prescription drugs represents the molecular basis for an important class of harmful drug interactions.

关 键 词：细胞色素P450 3A 孕烷X受体 药物代谢 

分 类 号：R345.99[医药卫生—基础医学] R392.11