我国大气颗粒物污染严重，细颗粒物（PM2.5）危害尤为突出，研究显示PM2.5与暴露人群慢性阻塞性肺疾病(COPD)的患病率和死亡率密切相关，但其诱发COPD的机制不清。课题组前期发现PM2.5可引起人正常肺上皮细胞（BEAS-2B）发生氧化应激，抗氧化调控基因Nrf2、Trx表达上调，伴有转录因子NF-κB和炎性因子IL-8的上调，提示PM2.5可能经Nrf2/Trx/NF-κB参与诱发BEAS-2B的炎症反应。本课题拟建立PM2.5诱导的大鼠COPD模型，分析大鼠肺功能、肺组织病理变化、COPD相关炎症因子的关系，探索PM2.5在COPD中的早期作用规律；体外细胞实验利用Nrf2过表达、干扰Trx入核、Transwell共培养等技术，探讨Nrf2/Trx/NF-κB通路在PM2.5致COPD的作用机制。该研究将为COPD的早期干预、早期诊断和治疗提供新思路，具有重要的公共卫生学意义。

Air pollution is quite serious in China nowadays especially due to fine particulate matter in the atmosphere (PM2.5). Epidemiological studies give evidence to prove that PM2.5 is associated with the increasing of prevalence and mortality on chronic obstructive pulmonary disease (COPD). However, the mechanisms are not fully understood. Our previous research found that PM2.5 exposure triggered oxidative stress in human pulmonary epithelial (BEAS-2B) cells and increased expressions of nuclear factor-E2-related factor-2 (Nrf2) and thioredoxin (Trx). Meanwhile, nuclear factor-kappa B (NF-κB) and inflammatory cytokine interleukin-8 (IL-8) were activated by PM2.5. These observations indicated that PM2.5 may induce inflammatory response through the Nrf2/Trx/NF-κB signaling pathway in BEAS-2B cells. In this project, COPD models induced by PM2.5 in rats would be established to determine whether PM2.5 facilitates COPD development. The correlation among lung function, pathological changes of lung tissue and levels of inflammatory cytokines in rats were analyzed. In vitro, experimental technologies such as overexpression of Nrf2, Transwell co-culture system and disturbed nuclear translocation of Trx would be used to explore the molecular mechanisms of Nrf2/Trx/NF-κB signaling pathway on PM2.5-induced COPD. The research would provide an innovative way and strategy for early intervention, diagnosis and therapy in COPD, which has great public health significance.