申请人既往研究发现吸烟所致肺血管内皮细胞凋亡是COPD的重要病理机制。外泌体是细胞间信息传递的载体，巨噬细胞外泌体可调控其他细胞的生物功能。但COPD中肺泡巨噬细胞外泌体对肺血管内皮细胞的作用尚不明确。课题组观察到香烟暴露后，肺泡巨噬细胞及其外泌体中miR-155增加，肺泡巨噬细胞上清液可促肺血管内皮细胞凋亡。研究报道miR-155可调控Nrf-2/HO-1通路介导细胞凋亡。申请人推测吸烟使肺泡巨噬细胞miR-155增加，通过外泌体作用于肺血管内皮细胞，抑制Nrf-2/HO-1通路，引起线粒体功能异常，导致肺血管内皮细胞凋亡，参与COPD的发生。本项目拟从人体、动物和细胞探讨：COPD患者及小鼠肺泡巨噬细胞外泌体中miR-155的表达；miR-155对COPD小鼠肺血管内皮细胞凋亡的影响；肺泡巨噬细胞外泌体miR-155调控肺血管内皮细胞凋亡的机制。为寻找COPD的治疗新途径提供依据。

The applicant's previous research found that smoking-induced abnormal apoptosis of pulmonary vascular endothelial cells is an important pathological mechanism of COPD, and alveolar macrophages also play an important role in the pathogenesis of COPD. Exosomes are important carriers for transmitting information between cells, and macrophage exosomes can regulate the biological effects of other cells. However, the role of alveolar macrophage exosomes on pulmonary vascular endothelial cells in COPD is not clear. The research team initially observed that after exposure to tobacco smoke, miR-155 increased in alveolar macrophages and released exosomes, and alveolar macrophage supernatant promoted apoptosis of pulmonary vascular endothelial cells. Research have reported that miR-155 can bind to Nrf-2 and regulate Nrf-2/HO-1 signaling pathway to mediate apoptosis. Applicants speculated that in COPD, miR-155 expression was up-regulated in lung macrophages, released by exosomes and released outside the cell and acted on pulmonary vascular endothelial cells, inhibiting the expression of Nrf-2/HO-1 signaling pathway, causing mitochondria dysfunction and causing apoptosis of pulmonary vascular endothelial cells, involved in the pathogenesis of COPD. This project is to be discussed from human, animal and cell: miR-155 expression in alveolar macrophages and exosomes in COPD patients and mice and apoptosis of pulmonary vascular endothelial cells; The effect of pulmonary macrophage exosomes miR-155 on apoptosis of pulmonary vascular endothelial cells in COPD model mice; The molecular mechanism of alveolar macrophage exosome miR-155 regulating apoptosis of pulmonary vascular endothelial cells. This project will provide experimental evidence for finding new ways to treat COPD.