慢性肺部炎症是慢性阻塞性肺疾病（COPD）的主要临床表现，其中肺泡巨噬细胞是其炎症进程的核心参与者。改善肺泡巨噬细胞功能，降低其介导的炎症损伤，是疾病防治的关键。我们研究发现：岭南特色中药化橘红的核心药效成分柚皮苷可靶向调控肺泡巨噬细胞，改善COPD慢性炎症与肺功能，其作用与抑制Caspase-1/IL-1β/IL-18轴有关，但具体机制未明。本研究以COPD模型小鼠与小鼠原代肺泡巨噬细胞为研究对象，①通过抑制Caspase-1轴，阐明柚皮苷调控COPD细胞焦亡的作用；②通过转录组学及后续验证，明确柚皮苷抑制肺泡巨噬细胞焦亡的机制；③通过巨噬细胞体内移植实验，验证“柚皮苷通过靶向抑制Caspase-1/IL-1β/IL-18介导的肺泡巨噬细胞焦亡，改善COPD炎性损伤和肺功能障碍”这一科学假说。本研究将为化橘红治疗COPD提供重要依据，并为以肺泡巨噬细胞焦亡为靶点的COPD防治提供新思路。

Chronic inflammation is a characteristic clinical manifestation of Chronic obstructive pulmonary disease (COPD), a process of which alveolar macrophage is crucially involved in. Thus, it is fundamental to maintain the functional integrity of alveolar macrophage while ameliorating alveolar macrophage mediated inflammation in the treatment of COPD. In our previous work, we found that naringin, one feature constituent of medicinal herb Huajuhong, can specifically target alveolar macrophages during lung inflammation and effectively attenuate pulmonary dysfunction and focal inflammation in COPD mice. The in vivo efficacy of naringin is tightly associated with its inhibitory actions on Caspase-1/IL-1β/IL-18 signaling, yet its detailed mechanisms remain obscured. Hence, in this proposal, by using cigarette smoke induced COPD mice and primary cultured mice alveolar macrophage, we aim to: (1) investigate the regulatory role of naringin on Caspase-1 dependent canonical pyroptosis in COPD; (2) unseal the mechanism of naringin on regulating alveolar macrophage pyroptosis by transcriptome sequencing and experimental validation; (3) use the in vivo alveolar macrophage transplantation mice model to prove the hypothesis that naringin protect against inflammatory injuries and pulmonary dysfunctions of COPD by specifically targeting Caspase-1/IL-1β/IL-18 mediated pyroptosis of lung alveolar macrophage. In conclude, our study will not only provide essential experimental basis for Huajuhong for treating COPD, but also shed light on a promising therapeutic strategy of targeting alveolar macrophage pyroptosis in the treatment of COPD that deserves further investigation.