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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。
Six-month-old C57BL / 6 mice of different sexes were divided into male and female (n = 6), and their livers were harvested respectively. The liver I phase metabolism was determined by real time quantitative PCR (RT-qPCR) The relative amount of enzyme mRNA expression. MRNA levels of 8 metabolic enzymes (Cyp2b9, Cyp4a14, Cyp2b10, Cyp2b13, Cyp4a10, Cyp2c38, Fmo3, Nqol) among the 24 phase I metabolic enzymes analyzed were highly expressed in the livers of female mice (P <0.01 or P <0.05 ). The mRNA levels of five metabolic enzymes (Cyp4a12, Cyp7b1, Cyp2d9, Fmo5 and Cess2c) were significantly higher in the liver of male mice (P <0.01 or P <0.05). Other I- There was no significant difference in mRNA expression. Studies have shown that gender differences significantly affect mRNA expression profiles of phase I metabolizing enzymes in the liver of mice, leading to individual differences in pharmacokinetics and pharmacodynamics of the drug.