有机磷系阻燃剂诱发潜在环境疾病及其机制研究

项目名称： 有机磷系阻燃剂诱发潜在环境疾病及其机制研究

项目编号： No.31670508

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 生物科学

项目作者： 李学彦

作者单位： 中国人民解放军北部战区总医院

项目金额： 25万元

中文摘要： 随着有机磷系阻燃剂（OPFRs）生产和使用的急剧增加，水体环境OPFRs污染与健康危害日益受到关注。针对这一上升的环境问题，课题首先以大鼠为模式生物，以饮用水体为暴露方式，以氯代/氯代基OPFRs为典型污染物，对大鼠进行染毒，通过行为指标、多巴胺能含量、多巴胺能神经元面积、Western blotting、活性氧、乙酰胆碱酯酶、线粒体复合物I、功能基因组学及代谢组学分析验证OPFRs是否能够诱发帕金森病的发生并揭示其诱发机理。进一步通过人体血清及尿液中代谢组学分析，筛选出脂肪肝和肝癌等疾病的分子标志物，同时，以大鼠为模式生物进行动物实验。随后通过人体和大鼠特定的肝脏羧酸酯酶CESs的测定和对比，探讨OPFRs是否导致高甘油三酯血症而引发脂肪肝，是否因改变其肝脏脂质代谢而诱发肝癌发生，并揭示其中的诱发机理。最终为我国OPFRs污染防治以及临床预防和治疗各类疾病发生与发展提供基础数据和科学依据。

中文关键词： 阻燃剂污染；代谢组学；健康风险分析；消化道肿瘤

英文摘要： With the dramatic increase in production and utilization of organophosphorus flame retardants (OPFRs), more and more attention has been paid to their water-environmental pollution and health hazards..For the rising environmental concerns, this project would use rat as a model organism, drinking water as exposure path, chlorinated/chlorine OPFRs as typical pollutants, to analyze the behaviors, dopamine content, dopamine neurons area, Western blotting, and reactive oxygen species, acetylcholinesterase, mitochondrial complex I and functional genomics and metabolomics to verify whether OPFRs could induced Parkinson's disease and reveal the related mechanisms. Through the analysis of metabolism in human serum and urine, the molecular markers of fatty liver and liver cancer were selected. At the same time, rats were tested. Subsequently, the measurements and comparisons of the human and rat specific liver carboxylesterase would be conducted to explore whether OPFRs induce hypertriglyceridemia, fatty liver and lead liver cancer due to the change of the liver lipid metabolism, and reveal the related mechanisms. The conduction of this project would provide basic data and scientific basis for the prevention and treatment of OPFRs pollution and the occurrence and development of various diseases in China.

英文关键词： Flame retardant pollution;Metabolomics;Health risk analysis;Digestive tract cancer