大气细颗粒物(PM2.5)污染，是我国当前环境保护和人民健康面临的突出问题。其中一个亟需阐明的科学问题是PM2.5在人类呼吸系统中的分布和对功能的影响, 即分子病理学的研究。本项目利用烟雾箱装置模拟细颗粒物污染，在精密控制的系统中进行小鼠暴露试验 （对污染物成分、浓度和暴露时间精确控制）。同时开展的实验中，小鼠暴露于城市环境空气（北京和上海）或者洁净空气中。之后利用免疫染色等生物化学或者分子生物学手段测定污染物在呼吸系统中的分布、肺组织的生理反应与损伤、以及基因表达和微生物谱的变化。利用这一实验设计，将分别研究成年和幼年小鼠，以揭示大气污染对成年人和青少年相同与异同的危害。本研究将为系统揭示大气细颗粒物对呼吸系统的影响提供科学实验基础；并量化污染物成分、浓度、暴露时间导致的肺组织生理变化。研究结果对防治与预测PM2.5污染对人民健康的危害有直接的指导作用。

Fine particles (e.g., PM2.5) are important components in air pollution among major Chinese cities, and attracted increasing concerns regarding to their adverse impact on human health, especially respiratory systems. However, the physiological consequences of high PM2.5 exposure remain understudied. The aims of the current research are to systematically characterize and quantify the physiological, cellular and molecular reactions in the respiratory system (airway and lung tissue) after PM2.5 exposure, in terms of pollutant composition, concentration and exposure time. To achieve these goals, we design an exposure-response study using mouse models. Animals will be exposed in (1) polluted air of major Chinese cities (Beijing and Shanghai); (2) smog box, where we accurately control pollutant composition and concentration; and (3) filtered clean air. Afterwards, the respiratory system of the study mice will undergo lung function tests and immune-staining assay to examine the physical locations of the immune cells in the airway. We also will investigate the molecular level changes (gene expression and microbiome) induced by PM2.5 exposure. Further, we leverage known disease signatures (e.g. COPD, astham or lung cancer) to inform the adverse effect. Following identical design, we will study both young and adult mice in parallel, reflecting conditions of human individuals at young and adult ages, respectively. This proposed project will provide quantitative and highly interpretable data on the physiological, cellular and molecular effect of PM2.5 exposure, and guidance on controlling air pollution as well as reducing the risks of human diseases.