慢性阻塞性肺疾病(慢阻肺)的发生与有毒有害气体颗粒对气道和肺部产生的炎症反应有关，发病机制尚不明确，缺乏有效的治疗方法。外泌体是细胞生理及病理状态下均可分泌的囊泡样小体，携带多种蛋白质、RNA参与细胞间通讯。研究表明，暴露于有害刺激会使肺上皮细胞来源外泌体分泌增强或成分改变。从慢阻肺、肺癌等模型中分离的外泌体可遗传宿主细胞的病理特性，参与疾病发展。本人前期研究发现，敲除干细胞中ALIX（囊泡形成相关蛋白）可减少外泌体分泌并降低其生物学功能，又发现随着慢阻肺疾病发展外泌体的分泌逐渐增多，但ALIX是否调控肺上皮细胞来源外泌体分泌而干预慢阻肺的发生发展却未可知。本课题拟基于前期工作基础，通过体内、体外实验探讨敲除ALIX是否可以减少慢阻肺状态下分泌的外泌体，及其对肺上皮细胞间异常通讯和整体肺损伤的影响，并阐明分子机制。这将进一步揭示慢阻肺的发病机制，从而为肺部相关疾病的诊断和治疗提供新的思路。

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses from toxic and harmful gas particles in the airways and lungs. The pathogenesis is still unclear, and there is a lack of simple and effective diagnostic and therapeutic methods. Exosomes are membranous particles that can be secreted by most cell types under normal or pathological conditions. Their proposed role as intercellular hormone-like messengers, together with their stability as carrier of proteins and RNA. Studies have shown that airway exposure to harmful stimuli can enhance the secretion or change the composition of the exosomes. Exosomes isolated from COPD, lung cancer and idiopathic pulmonary fiber models inherit the pathological characteristics of host cells and promote disease progression. Our previous research found that knockout ALIX, vesicle formation-related protein, in stem cells can reduce exosome secretion and reduce its biological function. And recently we found that ALIX is highly expressed in COPD lung tissue and cell model, but whether ALIX regulates exosome secretion in COPD pathological state and participates in the occurrence and development of disease is still unknown. Based on preliminary work, this project aims to explore whether knockout of ALIX can reduce exosomes derived from the COPD model, and its effect on pulmonary function and abnormal communication between airway or alveolar epithelial cells through in vitro and in vivo experiments, and to clarify the molecular mechanism. This will deepen new understanding of the pathogenesis of COPD and provide new ideas for the diagnosis and treatment of pulmonary diseases.