白杨素在雌雄小鼠肝肠S9中磺酸化结合反应的性别差异  

Gender differences of chrysin sulfation in mouse liver and small intestinal S9 fractions

作　　者：周一平[1] 周昱[1] 马颖林 蒋昆谕[1] 孟胜男[1] 

机构地区：[1]中国医科大学药学院,沈阳110122

出　　处：《中国新药杂志》2016年第3期323-327,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金(81173123);辽宁省自然科学基金(2013021080)

摘　　要：目的:研究性别差异对FVB小鼠肝肠S9介导的白杨素磺酸化结合反应的影响。方法:分别建立雌雄小鼠与白杨素肝肠S9的体外孵育体系,通过超高效液相色谱法(UPLC)与LC-MS/MS液质联用技术测定其代谢产物。采用Graph Pad Prism 5软件对检测结果进行处理与分析。结果:肝肠中代谢产物均为单磺酸化结合产物且均呈底物抑制的动力学特征,反应速率均存在显著的性别差异(P<0.05)。肝中雌鼠的代谢速率整体趋势高于雄鼠,而小肠中雌鼠的代谢速率明显低于雄鼠。结论:性别差异对白杨素的肝肠代谢动力学有显著性影响,这也许与雌雄小鼠代谢酶mRNA的表达有关。Objective： To investigate gender differences in the sulfation of chrysin in liver and intestinal S9 fractions from FVB mice. Methods： The incubation system of chrysinin in vitro was established in the tissue S9 fractions from mice. Ultra high performance liquid chromatography（ UPLC） was utilized to analyze chrysin and its corresponding sulfates. Mass spectrum（ MS） was employed to confirm the structural identification of the metabolites. Model fitting and parameter estimation were performed using the Graphpad Prism V5 software. Results：Chrysin formed one monosulfate in the liver and intestinal S9 fractions from FVB mice. The metabolic behavior of chrysin in the S9 fractions was followed substrate inhibition kinetics. The sulfation rate of chrysin in liver and intestinal S9 fractions from female and male mice had significant difference（ P〈 0. 05）. The sulfation rate of chrysin in the liver S9 fractions from female mice was higher than in those from males. However,such metabolic rate of chrysin catalyzed by intestinal S9 fractions from male mice was higher than by those from female mice. Conclusion：Gender differences strongly impacts sulfation of chrysin,which may be related to the mRNA expression of the metabolic enzymes in male and female mice.

关 键 词：白杨素 小鼠S9 磺酸化结合反应 性别差异 肝脏 小肠 

分 类 号：R96[医药卫生—药理学]