雌雄小鼠肝脏中I相代谢酶的mRNA表达谱  

mRNA Profiles for Phase I Metabolizing Enzymes in Livers of Male and Female Mice

作　　者：刘莹[1] 刘楠启[1] 王国丽[1] 韩龙[2] 孟胜男[2] 

机构地区：[1]中国医科大学基础医学院生物化学教研室,辽宁沈阳110001 [2]中国医科大学药学院药剂学教研室,辽宁沈阳110001

出　　处：《药物生物技术》2013年第5期381-385,共5页Pharmaceutical Biotechnology

基　　金：国家自然科学基金(No.81173123)

摘　　要：将6个月不同性别的C57BL/6小鼠分为雌、雄两组(n=6),分别取其肝脏,以荧光定量PCR(Real time quantitative PCR,RT-qPCR)测定肝脏中I相代谢酶mRNA的相对表达量。在分析的24个I相代谢酶中有8个代谢酶(Cyp2b9、Cyp4a14、Cyp2b10、Cyp2b13、Cyp4a10、Cyp2c38、Fmo3、Nqo1)的mRNA水平在雌性小鼠肝脏中高表达(P<0.01或P<0.05);5个代谢酶(Cyp4a12、Cyp7b1、Cyp2d9、Fmo5、Cess2c)的mRNA水平在雄性小鼠肝脏中表达较高(P<0.01或P<0.05);其它I相代谢酶在雌雄小鼠肝脏中的mRNA表达没有显著性差异。研究显示,性别差异显著影响小鼠肝脏中I相代谢酶的mRNA表达谱,这将导致药物在药动学和药效学方面的个体差异。Sex-based differences in drug metabolism are the primary cause of sex-dependent pharmacokinetics and reflect underlying gender differences in the expression of hepatic enzymes active in the metabolism of drugs. To reveal the possible molecular mecha- nisms of altered xenobiotic disposition and toxicity in individuals, mRNA profiles for phase I metabolizing enzymes were characterized in livers of male and female mice of 6 months of age. C57BL/6 mice were randomly divided into female group and male group （n = 6）, and the livers were collected. The relative mRNA expression of phase I metabolizing enzymes was examined by real time quantitative PCR （ RT-qPCR ） . Sex-based differences were investigated for 24 phase I metabolizing enzymes, and gender differences were observed. In female and male mice, mRNA levels for 8 phase I metabolizing enzymes （ e. g. , Cyp2b9, Cyp4al4, Cyp2bl0, Cyp2bl 3, Cyp4al0, Cyp2c38, Fmo3, Nqol ） were higher in female mice （ P 〈 O. 01 or P 〈 0.05 ） ,whereas mRNA levels for 5 phase I metabo- lizing enzymes （e. g. , Cyp4al2, Cyp7bl, Cyp2d9, FmoS, Cess2c） were higher in male mice （ P 〈 0. 01 or P 〈 0.05 ）. The mRNA levels for left enzymes （ Cypl al, Cyp2a4, Cyp2a5, Cyp3a41, Fmol, Cess3a, Por, Adh4, Aldh3a2, Aldh4al and Aldh6al ） showed the similar levels in both genders. Gender differences have significant effects on the mRNA expression profiles of phase I metabolizing enzymes in livers of mice, and it may characterize pharmacokinetics and pharmacodynamics of drugs and contribute to individual differences in drug efficacy and toxicity.

关 键 词：I相代谢酶 mRNA谱 C57BL 6小鼠 性别差异 荧光定量PCR 个体差异 

分 类 号：Q55[生物学—生物化学] Q522.2