大气细颗粒物PM1对人类健康的影响日益受到关注，但其引发呼吸道氧化损伤的病理学机理尚不十分清楚。最近研究发现，金属元素作为PM1的重要组成成分，对健康的影响不仅与其浓度有关，还与元素的化学形态密切相关。本项目以PM1中金属元素为切入点，拟利用电感耦合等离子体质谱（ICP-MS）、近边吸收精细结构谱（NEXAFS）和正矩阵因子分解法（PMF）分析PM1暴露小鼠肺组织中金属元素的浓度、化学形态和来源；结合分子细胞生物学技术手段，重点探讨miR34a、miR93调控抗氧化Nrf2/ARE信号通路在PM1金属元素诱导肺泡上皮细胞氧化应激效应的分子作用机制，阐明Nrf2/ARE通路中关键调控分子及效应基因的表达变化，进一步揭示PM1金属元素的化学形态与肺组织氧化损伤的关系，为PM1的毒性预防提供科学依据。

Airborne fine particles with a mean aerodynamic diameter of less than 1.0 μm (PM1), a component of air pollution, have been epidemiologically associated with pulmonary and cardiovascular diseases. However, the mechanisms underlying PM1 related oxidative stress in lung injury has not been fully elucidated. Recent studies have shown that the adverse effects of metal elements as major component of PM1 on human are not only related with the concentrations, but also chemical species. In this project, the concentrations, chemical species and sources of metals in the lung of PM1-treated mice will be detected and analyzed by inductively coupled plasma mass spectrometry (ICP-MS), near edge X-ray absorption fine sructure (NEXAFS) and positive matrix factorization method (PMF), respectively. Meanwhile, the underlying molecular mechanism of Nrf2/ARE signaling pathway are involved in PM1-induced Nrf2 nuclear translocation and enzymatic antioxidant defense in the lung alveolar epithelial cells will be investigated to explore the signaling pathway regulated by miR34a and miR93. Understanding the signaling pathways implicated in Nrf2-mediated defenses against PM1-induced oxidative stress will help develop new strategies for the prevention and treatment of pulmonary diseases associated with airborne pollution.