中国药理学与毒理学杂志2013,Vol.27Issue(3):406-410,5.DOI:10.3867/j.issn.1000-3002.2013.03.017
昆明种小鼠细胞色素氧化酶CYP1A基因表达的昼夜节律变化
Circadian rhythm variation of cytochrome CYP1A gene expression in liver of Kunming mice
摘要
Abstract
OBJECTIVE To examine circadian rhythm and sex variation of cytochrome P-450 1A1 (CYP1A1) and aryl hydrocarbon receptor (AhR) expression in the liver of Kunming (KM) mice.METHODS Adult KM mice were maintained in the SPF-grade animal facilities for 2 weeks,and livers were collected every 4 h during the 24 h period.Total RNA was isolated,purified,and subjected to reverse transcription (RT)-PCR analysis for expression of CYP1A1,AhR and clock genes.Paracetamol 500 mg· kg-1 was ip given another 20 mice at 6:00 and 18:00,and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined.RESULTS The expressions of AhR and AhR-regulated CYP1A11 and CYP1A12 peaked about 18:00 pm and reached the nadir about 6:00 am.Sexdifferences for AhR (6-fold for females and 7-fold for males),CYP1A11 (4-fold for females and 29-fold for males),and CYP1A12(3-fold for females and 5-fold for maes) were also evident.The circadian variation of CYP1A1 and AhR resembled the clock genes Rev-erbα,Per1 and Per2.Circadian rhythm of CYP1A1 expression influenced the hepatotoxicity of paracetamol,which is bioactivated by CYP1A1.CONCLUSION Circadian rhythm and sex variation of CYP1A1 and AhR were evident in the liver of KM mice,which could impact the pharmacology and toxicology of drugs such as paracetamol.关键词
细胞色素P450 CYP1A1/昼夜节律/性别特性/基因表达Key words
cytochrome P-450 CYP1 A1 / circadian rhythm/ gender identity/ gene expression分类
生物科学引用本文复制引用
金涛,张丹,徐懿乔,徐尚福,刘杰,陆远富..昆明种小鼠细胞色素氧化酶CYP1A基因表达的昼夜节律变化[J].中国药理学与毒理学杂志,2013,27(3):406-410,5.基金项目
The project supported by Guizhou Science and Technology Funds(2009-70019) (2009-70019)
Guizhou Scinece and Technology Pharmacokinetics Platform Project(2008-002) (2008-002)
and Guizhou Graduate Eduation Fund(023) (023)
贵州省科技厅国际合作基金(2009-70019) (2009-70019)
贵州省科技厅药物代谢动力学平台项目(黔科2008-002) (黔科2008-002)
贵州省研究生教育创新基地(023) (023)