典型环境污染物与超细颗粒低水平联合暴露的心血管毒性及机制研究

我国大气颗粒污染严重，超细颗粒（PM0.1）危害尤为突出，但目前超细颗粒与污染物联合作用及其与心血管疾病的关系尚无研究。本项目将实验室和人群心血管疾病样本研究相结合，构建超细颗粒与典型环境污染物的联合暴露体系并进行系统表征；确定体系在效应水平和低水平暴露的联合作用及类型；在体外和体内条件下研究联合暴露体系致心血管系统氧化损伤、DNA损伤、细胞周期、细胞凋亡、自噬、炎症反应和病理改变，确定联合体系心血管毒性效应；采用毒物基因组学技术进行高通量筛查和相关机制研究；开展人群心血管疾病病例对照研究和疾病易感性研究；分析心血管疾病形成过程中的环境遗传交互作用；筛选心血管疾病相关效应生物标志和疾病早期生物标志。根据实验室和人群研究结果，进行心血管疾病毒作用模式（MOA）和人类相关性框架（HRF）研究，综合分析联合暴露与人类心血管疾病的关联，为大气环境治理和心血管疾病病因学研究及有效防治提供科学依据。

The atmospheric particle pollution is very serious in China, especially ultrafine particle (PM0.1). However, up to nowthere has been no study on the joint action of ultrafine particles and pollutants and its relationship with cardiovascular disease. This project would combine the laboratory and cardiovascular disease sample research together, construct and systemic characterize the joint exposure system of ultrafine particles and typical environmental pollutants; determine the joint toxicity and its type under the effective-level and low-level exposure; investigate the oxidative damage, DNA damage, cell cycle, apoptosis, autophagy, inflammation and pathological changes of cardiovascular system induced by the joint exposure system in vitro and in vivo, and determine the cardiovascular toxicity; carry out the high throughput screening using the techniques of toxicogenomics and explore its related mechanisms; develop the case-control study and disease susceptibility research of population cardiovascular disease; analyze the envrionmental genetic interaction during the process of cardiovascular disease developing; and screen out the exposure biomarkers and disease biomarkers in early stage related to the cardiovascular disease. Based on the results acquired from the lab and population research, the mode of action (MOA) and human relevance framework (HRF) would be done, and the correlation between joint exposure and human cardiovascular disease would be analyzed comprehensively. The research achievement would provide the scientific basis for the atmospheric environmental management, the etiology research and the effective prevention and control of cardiovascular disease.