基于控制暴露人体实验探讨DNA甲基化在PM2.5心肺健康效应中的作用

项目名称： 基于控制暴露人体实验探讨DNA甲基化在PM2.5心肺健康效应中的作用

项目编号： No.81502775

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈仁杰

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 国外已有数篇研究报道PM2.5可以引起人体DNA甲基化水平出现异常，但是对于DNA甲基化在PM2.5健康效应中可能的作用仍不清楚，且研究结果并不一致。本课题拟通过双盲交叉设计的控制暴露人体试验，运用“真”、“假”空气净化器分别建立一个相对干净、相对污染的PM2.5暴露环境，在我国城市背景污染水平下探讨DNA甲基化在PM2.5致心肺健康效应中可能的介导作用或交互作用。本课题拟评估2个全基因组DNA甲基化指标、8个心肺功能基因的DNA甲基化，以及气道炎症、氧化应激、肺功能、心率变异性、血压、外周血炎症/凝血/微血管收缩指标等20多项心肺功能健康指标。同时，还比较和探讨了PM2.5的27种化学成分和6种来源对人体DNA甲基化的影响以及对PM2.5-DNA甲基化交互作用的影响。本课题预期研究结果对于深入理解PM2.5的致病机制，优化大气污染防控和公共卫生预防策略均具有重要意义。

中文关键词： 细颗粒物；DNA甲基化；心肺系统；双盲交叉设计；控制暴露试验

英文摘要： Several previous studies abroad suggested a link between PM2.5 exposure and abnormal human DNA methylation, but the investigations were quite limited regarding the role of DNA methylation in the cardiopulmonary effects of ambient PM2.5 and the existing evidence was inconsistent. The objective of this project is to explore the possible mediation and/or interaction roles of DNA methylation in the cardiopulmonary health effects of PM2.5 based on a controlled human exposure experiment with double-blinded randomized crossover design. True and sham indoor air purifiers are alternatively used to establish two drastically different exposure scenarios for PM2.5. We will evaluate 2 indicators for genome-wide DNA methylation, 8 functional genes for DNA methylation, and more than 20 indicators of cardiopulmonary health including airway inflammation, oxidative stress, lung function, heart rate variability, blood pressure, and circulatory inflammation, coagulation and vasoconstriction. Furthermore, we will analyze 27 chemical components and 6 kinds of sources of PM2.5, and evaluate their associations and potential interactions with DNA methylation. This project is expected to provide new insights into the underlying pathogenic mechanism of PM2.5, and to help design strategies for the control of PM2.5 and its public health prevention.

英文关键词： PM2.5;DNA methylation;cardiopulmonary system;double-blinded randomized crossover design;controlled exposure experiment