从分子机制到治疗靶点：线粒体自噬在慢性阻塞性肺疾病中的研究进展

From Molecular Mechanisms to Therapeutic Targets: Research Progress of Mitophagy in Chronic Obstructive Pulmonary Disease

摘要: 慢性阻塞性肺疾病(COPD)由有毒颗粒或气体暴露引发，全球疾病负担重。香烟烟雾等可致线粒体损伤，线粒体自噬失调是关键，涉及PINK1/Parkin等通路。其在发病初期起保护作用，进展期因通路受抑加剧损伤。目前，靶向线粒体自噬的治疗策略包括线粒体分裂抑制剂、罗氟司特、SIRT1激活剂等药物干预、基因治疗及物理治疗。线粒体自噬调控机制的异质性、动物模型局限性及靶向治疗的安全性等问题仍需解决。未来需深入解析调控网络，开发精准疗法，并结合抗炎、抗氧化策略，为COPD治疗提供新方向。

Abstract: Chronic obstructive pulmonary disease is triggered by exposure to toxic particles or gases and imposes a heavy global disease burden. Cigarette smoke and other factors can cause mitochondrial damage, and dysregulation of mitochondrial autophagy is a key factor, involving pathways such as PINK1/Parkin. In the early stage of the disease, it plays a protective role, but in the advanced stage, the inhibition of the pathway exacerbates the damage. Currently, therapeutic strategies targeting mitochondrial autophagy include drug interventions such as mitochondrial fission inhibitors, roflumi-last, SIRT1 activators, gene therapy, and physical therapy. Issues such as the heterogeneity of the mitochondrial autophagy regulatory mechanism, the limitations of animal models, and the safety of targeted therapy still need to be addressed. In the future, it is necessary to deeply analyze the regulatory network, develop precise therapies, and combine anti-inflammatory and antioxidant strategies to provide new directions for the treatment of COPD.