中国药理学通报2017，Vol.33Issue(2)：167-170,171,5.DOI:10.3969/j.issn.1001-1978.2017.02.005
药物代谢酶的个体发育及表观遗传调控
Ontogeny of drug metabolism enzymes and epigentic regulation
摘要
Abstract
Great changes in drug metabolizing enzyme (DME) expression occur in the fetus and child during development. Individual hepatic DME ontogeny can be categorized into one of three groups based on developmental trajectories.Some enzymes such as CYP3A7,are expressed at highest level in the fetus dur-ing the first trimester and either remain elevated or slightly de-crease during gestation,but are silenced or reduced to relatively low levels within one to two years after birth.SULT1 A1 is an ex-ample of the second group of DME.These enzymes are ex-pressed at relatively constant levels throughout gestation and into adulthood.CYP3A4 belongs to the third DME group .These en-zymes are expressed at negligible or low levels in the fetus.Sig-nificant increases in enzyme levels are exhibited within the first one to two years after birth.The epigenetic regulation refers to genomic modifications that do not involve changes in DNA se-quence and include DNA methylation,histone modifications, and non-coding RNAs.The epigenetic regulation mechanisms are responsible for the developmental expression of DME genes dur-ing liver maturation.This review will provide a summary of DME developmental expression profiles and reveal epigenetic mecha-nisms underlying variable drug metabolism and drug response. Thus,knowledge regarding DME ontogeny has permitted im-proved capability to predict drug disposition in pediatric pa-tients,which is crucial for improving drug dosing leading to opti-mal safety and efficacy in children.关键词
个体发育/药物代谢酶/表观遗传学/发育开关/组蛋白甲基化/核受体Key words
ontogeny/DME/epigenetics/developmental switch/histone methylation/nuclear receptor分类
医药卫生引用本文复制引用
何航,阚全程,张莉蓉..药物代谢酶的个体发育及表观遗传调控[J].中国药理学通报,2017,33(2):167-170,171,5.基金项目
国家自然科学基金资助项目 （）
