慢性阻塞性肺疾病（COPD）病程迁延，持续性气道炎症和反复急性加重可导致肺功能进行性下降。中性粒细胞过度活化及中性粒细胞胞外诱捕网（NETs）形成增多，是加重气道上皮损伤、介导肺组织破坏的重要病理环节。短链脂肪酸（SCFAs）是肠道菌群的重要代谢产物，一方面可经游离脂肪酸受体2（FFAR2，即G蛋白偶联受体43）调节还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶活性和活性氧（ROS）生成，另一方面可通过乙酰辅酶A（acetyl-CoA）代谢途径参与组蛋白修饰，共同调控NETs形成；该作用与SCFAs种类、浓度、作用时间及中性粒细胞状态有关。COPD患者及模型动物常伴有肠道菌群失调和SCFAs减少；研究发现，SCFAs减少与FFAR2表达下降、NETs形成增加并存，外源性补充乙酸和丙酸后，肺部炎症和组织损伤有所减轻。中医药治疗COPD重视肺脾同治、肺肠同调，部分方药可调节肠道菌群结构和SCFAs代谢、改善肠黏膜屏障功能，并抑制中性粒细胞活化和NETs形成。系统梳理SCFAs调控NETs形成的作用机制及其与COPD肺部炎症的关系，总结中药干预的相关研究进展，为COPD中医药防治提供参考。

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by persistent airway inflammation and recurrent acute exacerbations, leading to gradual decline in lung function. Excessive neutrophil activation and increased formation of neutrophil extracellular traps (NETs) are key pathological mechanisms contributing to airway epithelial injury and lung tissue damage. Short-chain fatty acids (SCFAs), important metabolites produced by gut microbiota, can modulate NADPH oxidase activity and reactive oxygen species (ROS) generation via free fatty acid receptor 2 (FFAR2, also known as G protein-coupled receptor 43), while also participating in histone modification through the acetyl-CoA metabolic pathway—both pathways jointly regulating NET formation. This regulation depends on SCFA type, concentration, duration of exposure, and the state of neutrophils. Patients with COPD and animal models often exhibit dysbiosis of the gut microbiota and reduced levels of SCFAs. Studies have shown that decreased SCFAs coexist with downregulated FFAR2 expression and enhanced NET formation; exogenous supplementation with acetate and propionate has been found to alleviate pulmonary inflammation and tissue injury. Traditional Chinese medicine (TCM) approaches to COPD emphasize simultaneous treatment of the lungs and spleen, as well as coordination between the lungs and intestines. Certain TCM formulas and herbs can modulate gut microbiota composition and SCFA metabolism, improve intestinal mucosal barrier function, and suppress neutrophil activation and NET formation. This review systematically summarizes the mechanisms by which SCFAs regulate NET formation and their relationship with pulmonary inflammation in COPD, along with recent advances in TCM interventions, providing insights for the prevention and treatment of COPD using traditional Chinese medicine.

R285.5

国家自然科学基金地区项目［82560895］；贵州省科技计划项目中药、民族药大品种二次开发（黔科合重大（2025）14）；贵州省科技计划项目中医药防治急性呼吸系统疾病应用基础研究贵州省科技创新领军人才工作站（黔科合平台KXJZ[2025]041）；贵州中医药大学藏象理论与肠道菌群转化医学科技创新人才团队建设（贵中医TD合字[2023]002号）