酰胺类手性农药的立体选择性体外代谢组学研究

项目名称： 酰胺类手性农药的立体选择性体外代谢组学研究

项目编号： No.21207158

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 环境化学

项目作者： 朱文涛

作者单位： 中国农业大学

项目金额： 26万元

中文摘要： 手性农药立体选择性代谢行为的相关研究已有很多报道，但是对有关对映体单体在人和其它非靶标生物体内的完整代谢途径、代谢途径的差异、主要代谢物的定量分析及立体选择性代谢机理还缺乏系统研究。本研究将代谢组学的研究理念和策略引入到手性农药立体选择性代谢研究领域，以手性酰胺类农药甲霜灵和苯霜灵为受试农药，以人和大鼠肝微粒体和原代肝细胞为体外模型，利用代谢组学之代谢轮廓分析方法检测各对映体代谢物及其含量变化，研究代谢物随时间的变化规律及对映体间的选择性代谢差异，并探讨产生选择性代谢差异的机理；此外，还利用体外代谢方法制备稳定同位素标记的代谢物标准品，以此标准品为对照物，利用质谱对代谢物进行再次确认和精确的定量分析。本研究将手性农药代谢轮廓分析、立体选择性代谢机理研究、肝细胞毒性分析、种属差异以及性别差异分析相结合，为系统评价手性农药对人和其它高等生物的风险提供了依据。

中文关键词： 手性农药；代谢组学；立体选择性；同位素标记；

英文摘要： There are a lot of reports about the stereoselective metabolism of chiral pesticides in biological samples, but it's lack of systemic research on the optical pure enantiomer's behavior in the human and the other non-target organisms, such as their whole metabolic pathway, the differences of their pathway,the quantification analysis of their main metabolites and the stereoselective metabolism mechanism. In this proposal, the metabolomics concepts and strategies are introduced into the investigation field of the stereoselective metabolism of chiral pesticides and their enantiomers. Chiral amide pesticide metalaxyl and benalaxyl are selected as test pesticides, the human and rat liver microsomes or their primary hepatocytes are used as the in vitro model, the metabolite profiling strategy is used to detect the metabolites of each enantiomer and the changes of their concentrations. Meanwhile, this method is also used to investigate the time course of changes of the metabolites、the differences of the enantioseletive metabolism of the test pesticide's single enantiomer and the mechanisms of the stereoselective metabolism. Moreover, the isotope labeled metabolites produced by in vitro incubation will be used as the standard references for identification of the same compounds we found in the unlabeled incubations, they

英文关键词： chiral pesticides；metabolomics；stereoselectivity；isotope label；