慢性阻塞性肺疾病中程序性细胞死亡的 研究进展

Research Progress on Programmed Cell Death in Chronic Obstructive Pulmonary Disease

摘要: 慢性阻塞性肺疾病(COPD)是一种以气流受限为特征的进行性肺部疾病，其发病机制复杂，涉及多种细胞和分子过程。程序性细胞死亡(PCD)，包括细胞凋亡、铁死亡、细胞焦亡、自噬、铜死亡、泛凋亡、失巢凋亡和坏死性凋亡等，在COPD的发生发展中扮演着关键角色。香烟烟雾等有害刺激因素可诱导肺部结构细胞(如肺泡上皮细胞和内皮细胞)发生PCD，导致肺实质破坏和气道重塑，最终引起气流受限。深入理解COPD中不同PCD的机制，以及它们与炎症、氧化应激和纤维化等其他病理过程的相互作用，对于开发新的诊断和治疗策略至关重要。目前，针对PCD通路中关键分子和信号通路的调控已成为COPD治疗研究的热点，一些潜在的生物标志物和治疗靶点也逐渐被发现。靶向干预氧化应激和表观遗传调控通路可能成为潜在治疗策略，故本综述对近年来关于COPD中PCD的作用机制、潜在治疗靶点进行讨论。

Abstract: Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by airflow limitation, with a complex pathogenesis involving multiple cellular and molecular processes. Programmed cell death (PCD), including apoptosis, ferroptosis, pyroptosis, autophagy, cuproptosis, panoptosis, anoikis, and necroptosis, plays a critical role in the onset and progression of COPD. Harmful stimuli such as cigarette smoke can induce PCD in structural lung cells—including alveolar epithelial cells and endothelial cells—leading to parenchymal destruction and airway remodeling, ultimately resulting in airflow limitation. A deeper understanding of the distinct mechanisms underlying each form of PCD in COPD, as well as their interactions with other pathological processes—including inflammation, oxidative stress, and fibrosis—is essential for developing novel diagnostic and therapeutic strategies. Currently, modulation of key molecules and signaling pathways within programmed cell death (PCD) pathways has become a major focus in COPD therapeutic research, and several potential biomarkers and therapeutic targets have been progressively identified. Targeted interventions against oxidative stress and epigenetic regulatory pathways represent promising therapeutic strategies; therefore, this review discusses recent advances in the mechanistic roles of PCD in COPD and its potential therapeutic targets.