流行性病学和体内、外实验表明：环境内分泌干扰物引起的机体内分泌紊乱可能是糖代谢异常的一个重要诱因。拟除虫菊酯农药是一类具有对映体选择性的内分泌干扰物。因此，我们推测这类化合物也会对生物体正常糖代谢平衡产生不良影响，其代谢干扰效应也具有对映体选择性。但是，到目前为止，从手性层面研究其对机体糖代谢紊乱的选择性作用及机制仍处于空白。本项目拟选择高效氯氰菊酯及其对映体为研究对象，首先，通过双荧光报告基因法确定其内分泌干扰对映体选择性。随后，以人体真实污染负荷为依据，基于体内和体外实验设计，利用毒理代谢组学阐明各对映体代谢表型变化的主要代谢通路和相关毒作用模式；基于锁定的相关通路，利用荧光定量PCR等方法，在分子、细胞和动物个体水平，开展基于对映体选择性的高效氯氰菊酯对幼鼠糖代谢平衡影响及其分子机制研究。本项目研究结果有助于丰富手性农药潜在健康风险的研究内容，为高效安全农药的开发提供数据支持。

Epidemiological and in vivo and vitro experiments all revealed that endocrine disorder is one of the most important inducements. Previously, synthetic pyrethroids had been proved their enantioselectivity in endocrine disrupting in many studies. Therefore they may be a kind of potential risk factors in metabolic disorders diseases. However, data about the effect on glucose metabolism and its potential mechanism of chiral pesticides remains scare. Herein, beta-cypermethrin and its enantiomer were firstly selected to study their enantioselectivity on endocrine disrupting effects via various nuclear receptors . Then both the in vitro and in vivo studies will be designed to illustrate the systemic metabolomics and other biological changes related mode of action (MOA) induced by the pairing enantiomers. In addition, PCR, western blot and siRNA will be used to explore the potential mechanism of chiral cypermethrinin on glucose metabolism on the illustrated major MOA. This project can not only help to illustrate the enantiomers’ effects on glucose metabolism and their subtle mechanism difference, but also will be helpful to enrich theoretical foundation and data for developing the environment-friendly pesticides.