巨噬细胞(Mφ)极化引起的M1/M2表型变化在慢性阻塞性肺疾病（慢阻肺）炎症反应调控中发挥重要作用，外泌体miRNA通过靶基因调控Mφ极化影响慢阻肺发生发展，但其信号转导机制亟待阐明。我们前期研究发现，慢阻肺患者外周血miR-125a-5p及外泌体表达均上调，人支气管上皮细胞系miR-125a-5p过表达促进Mφ向M1极化，生物信息学预测miR-125a-5p与白介素1受体拮抗剂（IL1RN）存在靶向关系。本项目拟在慢阻肺患者、香烟烟雾暴露的支气管上皮细胞系和动物模型中，运用细胞转染、miR-125a-5p工具阻断剂等干预手段，研究外泌体miR-125a-5p对Mφ极化的影响及效应靶点，同时探索Mφ极化过程中炎症信号通路及细胞表型变化，验证“高表达的外泌体miR-125a-5p可能靶向IL1RN调控Mφ向M1极化，促进慢阻肺炎症反应”的研究假说。研究结果有助于为慢阻肺治疗提供新思路。

Changes in M1/M2 phenotypes caused by macrophage (Mφ) polarization play an important role in regulating the inflammatory response of chronic obstructive pulmonary disease (COPD). Exosomal microRNA influences the development of COPD by regulating macrophages polarization via its targeting genes. However, their signal transduction mechanisms need to be clarified urgently in COPD. Our previous studies found that the expression of miR-125a-5p and exosomes in peripheral blood of patients with COPD was up-regulated, and over-expression of miR-125a-5p in human bronchial epithelial cell line promoted Mφ to M1 polarization. Bioinformatics predict that there is a targeting relationship between miR-125a-5p and interleukin-1 receptor antagonist (IL1RN). The project in COPD patients, the primary bronchial epithelial cell lines and animal models of cigarette smoke exposure, is intended to observe the effect of exosomal miR-125a-5p on macrophage polarization and its target, and explore the changes of inflammatory signaling pathway and cell phenotype during the process of macrophage polarization, by using cell transfection, miR-125a-5p tool blockers and other intervention methods. The aim is to verify the hypothesis that high-expressed exosomal miR-125a-5p targeting IL1RN may regulate macrophage polarization to M1, and then promote inflammatory response of COPD. The study will be helpful to provide new ideas for COPD treatment.