线粒体自噬在动脉型肺动脉高压中作用的研究进展

doi:10.3969/j.issn.1674-8115.2025.12.011

摘要/Abstract

摘要：

动脉型肺动脉高压（pulmonary arterial hypertension，PAH）是一种病因复杂的心肺疾病，其主要特征是肺小动脉持续性收缩和重构，导致肺动脉压持续升高，进而引发右心室重构和最终的右心室衰竭。尽管当前的临床治疗主要通过靶向血管收缩-舒张失衡缓解患者临床症状，然而总体预后仍然较差，死亡率持续升高，亟需新的治疗策略。线粒体是细胞主要能量来源，通过氧化磷酸化（oxidative phosphorylation，OXPHOS）合成ATP，但在此过程中会产生活性氧（reactive oxygen species，ROS），诱发蛋白质、脂质和DNA损伤并加剧功能障碍。线粒体自噬作为维持细胞内稳态的重要机制，有助于识别并清除受损线粒体，保障细胞内能量代谢的平衡。近年来的研究表明，线粒体自噬在PAH发生发展中的作用具有两面性：一方面，线粒体自噬可能在PAH早期阶段被适度激活，清除受损线粒体并抑制细胞异常增殖；另一方面，随着PAH的进展，线粒体自噬被过度激活，各种细胞的异常增殖导致肺血管和右心室重构。该文通过检索近年来的相关文献，阐述在PAH不同阶段，线粒体自噬在肺血管和右心室重构中的作用，旨在为开发更有效的PAH干预手段提供理论依据。

关键词: 动脉型肺动脉高压, 线粒体自噬, 血管重构, 右心室重构

Abstract:

Pulmonary arterial hypertension (PAH) is a complex cardiopulmonary disease characterized by persistent constriction and remodeling of the pulmonary arterioles, leading to sustained elevation of pulmonary arterial pressure, right ventricular remodeling, and ultimately right heart failure. Although current clinical therapies mainly alleviate symptoms by targeting the imbalance between vasoconstriction and vasodilation, the overall prognosis remains poor and the mortality rate continues to rise, highlighting the urgent need for novel therapeutic strategies. Mitochondria serve as the primary energy source for cells, generating ATP through oxidative phosphorylation (OXPHOS). However, this process generates reactive oxygen species (ROS), which can damage proteins, lipids, and DNA, thereby exacerbating cellular dysfunction. As a crucial mechanism for maintaining cellular homeostasis, mitophagy facilitates the recognition and clearance of damaged mitochondria, thereby ensuring balanced cellular energy metabolism. Recent studies have revealed a dual-faceted role of mitophagy in the pathogenesis and progression of PAH. On the one hand, mitophagy may be moderately activated during the early stages of PAH to clear damaged mitochondria and suppress abnormal cell proliferation; on the other hand, with PAH progression, excessive mitophagy activation occurs alongside abnormal proliferation of various cell types, leading to pulmonary vascular and right ventricular remodeling. This paper reviews recent literature to elucidate the role of mitophagy in pulmonary vascular and right ventricular remodeling at different stages of PAH, aiming to provide a theoretical basis for developing more effective therapeutic interventions for PAH.

Key words: pulmonary arterial hypertension (PAH), mitophagy, vascular remodeling, right ventricular remodeling

中图分类号:

R543.2

范冰彬, 何玉虎. 线粒体自噬在动脉型肺动脉高压中作用的研究进展[J]. 上海交通大学学报（医学版）, 2025, 45(12): 1654-1661.

FAN Bingbin, HE Yuhu. Research progress on the role of mitophagy in pulmonary arterial hypertension[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(12): 1654-1661.

图/表 2

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