脂质过氧化在汽车尾气致肺损伤过程中的作用机制研究

项目名称： 脂质过氧化在汽车尾气致肺损伤过程中的作用机制研究

项目编号： No.81472955

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 宾萍

作者单位： 中国疾病预防控制中心职业卫生与中毒控制所

项目金额： 70万元

中文摘要： 汽车尾气（VE）是城市大气污染的主要来源，也是职业环境中的常见污染物。研究汽油和柴油发动机尾气致肺损伤的机制，对制定暴露标准和预防控制对策有重要意义。本项目拟以人肺细胞直接暴露整体VE气-液界面染毒方式为基础，以脂质过氧化（LPO）特异性产物为研究切入点，建立VE致肺损伤的实验室研究手段。重点针对8-iso-PGF2α、MDA&TBARS、4-HNE 等LPO特异性产物，探讨LPO在VE致肺损伤过程中的关联性、灵敏性和特异性。分析LPO特异性产物与炎性和遗传物质损伤标志物之间的量效关系，从致炎和遗传物质损伤的通路阐述LPO对肺细胞的调控机制。最后，在VE职业环境中开展分子流行病学研究，综合分析LPO特异性产物与环境暴露、内暴露、人群健康结局及炎性和遗传物质损伤指标的关系。结合实验室机制研究和人群数据，筛选出可评价VE致肺损伤的LPO生物标志物，为早期保护VE暴露人群提供科学依据和技术手段。

中文关键词： 汽车尾气；肺损伤；氧化应激；脂质过氧化；气-液界面

英文摘要： Vehicle exhaust (VE) is not only a major source of atmospheric pollution in city, but also a common pollutant in the occupational environment. Mechanism of lung injury induced by the gasoline and diesel engine exhaust, is of great significance to develop exposure standards and policies of prevention and control.This project intends to establish a method studying on lung injury induced by VE in laboratory, in which it will base on the air-liquid interface (ALI) technique of human lung cells directly exposed to the whole VE, and the specific products of lipid peroxidation (LPO) will be as the research point.It will probe into the relationship, sensitivity and specificity about the effect of LPO on lung injury induced by VE, which will focus on the specific product of LPO, e.g. 8-iso-Prostaglandin F2α (8-iso-PGF2α), malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS), 4-hydroxynonenal(4-HNE) and so on.To explore the regulation mechanism of LPO on lung cells through the pathway of inflammation and genetic damage, we will analyize the dose-effect relationship between specific products of LPO and the biomarkers of inflammatory and genetic damage. Finally, to validate and to explore the feasibility of LPO biomarkers, a molecular epidemiological study among the occupational population exposure to VE will be adopted, which will include a comprehensive analysis of the association of specific products about lipid peroxidation and environmental exposure characteristics, and internal exposure biomarkers, and population health outcomes, as well as inflammatory and genetic damage biomarkers. Combined with the mechanisms of laboratory study and the data of molecular epidemiological study on occupational population, we will screen the feasible biomarkers of LPO in the process of VE induced lung injury. And then, it will provide scientific basis and techniques for the early protection of VE exposed population.

英文关键词： Vehicle exhaust(VE);Lung injury;Oxidative stress;Lipid peroxidation(LPO);Air-liquid interface(ALI)