在慢阻肺发病过程中，线粒体自噬是一把双刃剑，其对慢阻肺的保护或加重作用取决于激活程度，而该程度主要由活性氧诱导的氧化应激强度决定。细颗粒物（PM2.5）是引起慢阻肺急性加重的主要非感染因素，其致病原理在环境污染严重的背景下亟待研究。我们前期研究发现，稳定期慢阻肺与雾霾期慢阻肺急性加重患者相比，后者血液中氧化应激加剧，且上皮细胞中NOX4/Nrf2氧化失衡更显著；体外PM2.5可显著降低线粒体膜电位、诱导上皮细胞活性氧产生、线粒体自噬和细胞凋亡。因此我们推测PM2.5可能通过诱导NOX4/Nrf2氧化失衡介导线粒体自噬过度激活，诱发慢阻肺急性加重。本课题拟研究PM2.5对氧化失衡和线粒体自噬过度激活的诱导作用及其关系；进一步拟建立PM2.5诱导的原代上皮细胞和小鼠慢阻肺急性加重模型，采用Nrf2 RNA干扰或敲除小鼠，确定PM2.5诱导慢阻肺急性加重的效应靶点和相关机制，为其防治提供新思路。

In the pathogenesis of chronic obstructive pulmonary disease (COPD), mitophagy is a double-edged sword for whether it is protective or aggravating in COPD depend on its level of activation, while such level is determined by intensity of ROS-induced oxidative stress. Fine particulate matter (PM 2.5) is one of the most important noninfectious factors of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), its mechanism of action is urgent to be studied. Our preliminary research has shown that compared to stable COPD patients, AECOPD patients during the haze period had anabatic oxidative stress in blood samples, and more obvious NOX4/Nrf2 oxidative imbalance in the bronchial epithelial cells; moreover, PM 2.5 markedly increased overproduction of ROS, reduced mitochondrial membrane potential (MMP), and induced mitophagy and apoptosis in vitro. Therefore, we speculate that PM2.5 may aggravate oxidative imbalance of NOX4/Nrf2 to induce excessive mitophagy, and then lead to AECOPD. The project is intended to firstly observe whether PM 2.5 can induce oxidative imbalance and excessive mitophagy, as well as the relationship between them, futhermore, we intended to establish PM2.5 induced primary epithelial cell and mouse models of AECOPD, and applied Nrf2 RNA interference and Nrf2 knockout mice to determine the target and mechanisms of PM2.5-induced AECOPD. The present study will provide new ideas for the prevention and treatment of PM2.5-induced AECOPD.