肺泡巨噬细胞极化在气道重塑中起重要作用，寻找肺泡巨噬细胞极化的启动机制和早期阻断办法是抑制COPD小气道重塑的关键环节。我们前期研究证实了表观调控分子miR-27-3p通过靶向结合PPARγ，介导肺泡巨噬细胞极化，但其对COPD小气道重塑的作用及机制尚不清楚。综合既往研究我们推测：miR-27-3p/PPARγ信号轴通过改变M1/M2型肺泡巨噬细胞极化平衡，参与COPD小气道重塑的形成。本项目拟从临床研究、体外机制探讨及动物模型靶点验证三方面共同探讨调控肺泡巨噬细胞极化的miR-27-3p/PPARγ信号轴对COPD小气道重塑的作用机制。该项目的实施将有助于阐明肺泡巨噬细胞参与COPD小气道重塑的表观调控机制，为确立miR-27-3p/PPARγ作为COPD治疗的新靶标提供科学依据。

Alveolar macrophage polarization plays an important role in airway remodeling. Finding the priming mechanism and early blocking methods of alveolar macrophage polarization are key links in inhibiting small airway remodeling of COPD. Our previous study confirmed that miR-27-3p, one apparent regulatory molecule, led to alveolar macrophage polarization through targeted PPARγ. But its role and mechanism of small airway remodeling in COPD are still unclear. Synthesizing previous studies, we speculate that miR-27-3p/PPARγ signaling axis is involved in the formation of small airway remodeling in COPD by altering the differentiation balance of M1/M2 alveolar macrophage. This project aims to explore the mechanism of miR-27-3p/PPARγ signaling axis regulating alveolar macrophage polarization on small airway remodeling in COPD from three aspects: clinical study, in vitro mechanism exploration and in vivo target verification. The implementation of this project may help clarify the apparent regulatory mechanism of alveolar macrophage involved in small airway remodeling of COPD and provides a scientific basis for establishing miR-27-3p/PPARγ as new targets for the treatment of COPD.