PFOS暴露致子代大鼠糖代谢异常的内质网应激机制研究

项目名称： PFOS暴露致子代大鼠糖代谢异常的内质网应激机制研究

项目编号： No.81202228

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 肖静

作者单位： 南通大学

项目金额： 23万元

中文摘要： 全氟辛烷磺酸（PFOS）是新型持久有机污染物，具有生物蓄积性及发育毒性。研究发现PFOS血清水平与人群高血糖、胰岛素抵抗正相关，可能是糖尿病尤其青少年发病率增高的危险因素，但内在机制不明。内质网应激与糖代谢异常、糖尿病发生关系密切，但在PFOS暴露所致糖代谢改变中作用未见报道。因此本研究拟以环境广泛存在而毒性机制尚不明确的PFOS为研究对象，以Wistar大鼠为实验动物，通过不同剂量发育期暴露，从宏观毒性终点效应到微观基因、蛋白表达变化多层次、系统阐明以下科学问题：① PFOS对子代糖代谢的影响，确定时间-剂量-效应关系。② PFOS对子代内质网应激影响及表观遗传学机制。③PFOS暴露中，子代糖代谢异常的内质网应激调节机制。研究结果有助于阐明低浓度PFOS对子代糖代谢的影响及作用机制 ，揭示其潜在糖尿病致病性，为正确评估环境中该类化合物对人体健康的影响提供科学依据。

中文关键词： 全氟辛烷磺酸盐；；持久性有机污染物；；发育毒性；；内质网应激；；糖代谢；

英文摘要： PFOS is a new kind of persistent organic pollutants, which is bioaccumulative and toxic to mammalian offsprings. Scientific evidences have proven that a positive correlation exists between PFOS exposure and hyperglycemia and insulin resistance. It is speculated that exposure to PFOS may be a risk factor for diabetes and other glucose metabolism disorders, especially in young people. However, the underlying mechanism is not clear. Although it is repoted that endoplasmic reticulum stress response plays an important role in the glucose metabolism disturbances and diabetes, so far there is no investigation about the relationship of the endoplasmic reticulum stress response and the abnormal glucose metabolism during the PFOS exposure. The purpose of this study is threefold: First, to describe the effects of the PFOS exposure on the glucose homeostasis in rat offsprings；second，to investigate the association between the endoplasmic reticulum stress response and the PFOS exposure; third, to explore the role of the endoplasmic reticulum stress response in the glucose metabolism disorders during the PFOS exposure，so as to evaluate the potential health effects and provide experimental and theoretical foundation for the chemical compounds.

英文关键词： PFOS;；POPs;；developmental toxicity;；endoplasmic reticulum stress;；glucose metabolism;