脂质过氧化在汽车尾气致肺损伤过程中的作用机制研究

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.

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。

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。研究汽车尾气致肺损伤的作用机制，对制定暴露标准和预防控制对策有重要意义。本项目围绕汽车尾气这一备受社会关注的职业与环境污染物，采用体外实验研究和职业暴露人群相结合的技术路线，应用人肺细胞直接暴露整体汽车尾气的气-液界面染毒技术作为关键的研究手段，在分析汽车尾气主要成份的基础上，研究了汽车尾气致肺细胞损伤的程度和脂质过氧化水平及其抗氧化防御系统关键酶系活性，再进而从细胞炎症因子的通路上研究了脂质过氧化在汽车尾气致肺损伤过程中的作用及其机制。最后，在职业暴露人群研究中，以脂质过氧化特异性产物（MDA、4-HNE和8-iso-PGF2α）为研究切入点，探讨了脂质过氧化特异性产物与肺功能降低的关联性、灵敏性和特异性，及其与尿中总羟基-多环芳烃的水平、染色体损伤、细胞炎症因子等的关系，进一步验证了脂质过氧化在致肺损伤中的作用，在职业暴露人群中筛选出了可评价作业工人暴露水平的脂质过氧化生物标志物，为早期保护汽车尾气暴露人群提供了科学依据和技术手段，并为汽车尾气致环境污染的综合防治提供一些线索。. 本课题执行期间，发表标注论文6篇，其中SCI论文2篇。该研究结果为将来开展的职业暴露汽车尾气的健康风险评估提供了重要的基础资料。为推进体外吸入毒理学研究，筛选可吸入性颗粒物或气溶胶等有害因素致肺损伤的生物标志物提供了可行的研究手段，为汽车尾气的暴露组学健康效应研究提供了重要的基础数据。