大气污染细颗粒物对特发性肺纤维化的影响及其分子机制研究

Atmospheric fine particulate matter is an aerodynamic diameter equal to or less than 2.5 micron fine particles, due to their small diameter, large surface area, chemical composition is complex, easy-enriched air toxic and harmful substances, also known as PM2.5. Idiopathic pulmonary fibrosis is characterized by pulmonary interstitial abnormal deposition of collagen fibers, continuously disruption of the lung parenchyma and decreased lung function with unkown cause. There is no specific treatment without lung transplantation. Our preliminary studies showed that there is deposition of PM2.5 in IPF patient's lung tissue. PM2.5 can activate ROS and TGF-β signaling pathway. PM2.5 can trigger inflammation and fibrosis in IPF mice model. In this study, we will investigate the constitution of PM2.5 and its interaction with human body. We will try to elucidate the molecular mechanism of PM2.5 on IPF. We will also investigate the interventional effect of NAC. This study can provide more information and evidence for the effects of PM2.5 on pulmonary diseases (especially IPF). There is important application prospect and scientific value.

大气细颗粒物是直径等于或小于2.5微米的细小颗粒，由于其直径细小、比表面积大、化学组成复杂、易于富集空气中的有毒有害物质，PM2.5被科学界公认是大气环境中健康危害最大的污染物。特发性肺纤维化是不明原因引起的一种以肺间质胶原纤维异常沉积，肺实质不断破坏，肺功能逐渐下降的疾病，病死率高，目前除了肺移植，无其他特效治疗方法。我们前期研究表明，IPF患者肺组织存在PM2.5沉积，细胞实验证明PM2.5可激活氧化应激及TGF-β通路，PM2.5可加重肺纤维化模型小鼠炎症及纤维化。本项目将重点研究空气中PM2.5的主要化学组成及其与机体的交互作用，阐明PM2.5主要组分对肺部炎症反应的影响进而导致IPF发生及急性加重的分子机制，探索NAC干预PM2.5所致IPF急性加重的效果及机制，为防治、临床干预PM2.5所致肺部疾病特别是IPF提供理论及科学依据，具有重要的应用前景及科学技术价值。

大气细颗粒物是直径等于或小于2.5微米的细小颗粒，由于其直径细小、比表面积大、化学组成复杂、易于富集空气中的有毒有害物质，PM2.5被科学界公认是大气环境中健康危害最大的污染物。特发性肺纤维化是不明原因引起的一种以肺间质胶原纤维异常沉积，肺实质不断破坏，肺功能逐渐下降的疾病，病死率高，目前除了肺移植，无其他特效治疗方法。我们前期研究表明，IPF患者肺组织存在PM2.5沉积，细胞实验证明PM2.5可激活氧化应激及TGF-β通路，PM2.5可加重肺纤维化模型小鼠炎症及纤维化。本项目将重点研究空气中PM2.5的主要化学组成及其与机体的交互作用，阐明PM2.5主要组分对肺部炎症反应的影响进而导致IPF发生及急性加重的分子机制，探索NAC干预PM2.5所致IPF急性加重的效果及机制。发表标注项目资助号的SCI论文12篇，其中第一作者1篇；协助培养研究生3人。项目成果有望为防治、临床干预PM2.5所致肺部疾病特别是IPF提供理论及科学依据，具有重要的应用前景及科学技术价值。