线粒体自噬在间充质干细胞干性维持及心血管疾病中的研究进展
Research Progress of Mitophagy in Stemness Maintenance of Mesenchymal Stem Cells and Cardiovascular Diseases
摘要: 线粒体自噬是维持线粒体质量和细胞代谢稳态的重要机制,可通过选择性清除受损线粒体,减少活性氧积聚及线粒体DNA外泄。近年来的研究表明,线粒体自噬不仅参与心血管疾病的发生发展,也与间充质干细胞(MSCs)的自我更新、多向分化和旁分泌功能密切相关。本文在概述PINK1-Parkin通路及BNIP3/NIX、FUNDC1等受体介导通路的基础上,重点梳理线粒体自噬在MSCs干性维持以及心力衰竭、心肌缺血再灌注损伤、心肌病、动脉粥样硬化、代谢性心血管疾病和心血管衰老中的作用。进一步结合现有研究,讨论CSE/H2S信号调控线粒体自噬并影响MSCs生物学特性的可能机制,以及药物干预、细胞预处理和靶向递送等潜在应用。当前,该领域仍面临自噬通量评价困难、作用具有细胞和病程特异性、干预窗口不明确等问题。阐明CSE/H2S–线粒体自噬–MSCs干性之间的关系,有望为优化MSCs制备及提高其心血管疾病治疗效果提供新的思路。
Abstract: Mitophagy is an essential component of mitochondrial quality control. By selectively removing damaged mitochondria, it limits excessive reactive oxygen species production and mitochondrial DNA release, thereby contributing to cellular homeostasis. Accumulating evidence indicates that mitophagy is involved not only in the pathogenesis of cardiovascular diseases but also in the maintenance of mesenchymal stem cell (MSC) stemness, including self-renewal, multilineage differentiation, and paracrine activity. This review summarizes the major molecular pathways of mitophagy, with emphasis on the PINK1-Parkin pathway and receptor-mediated mechanisms involving BNIP3/NIX and FUNDC1. We further discuss the roles of mitophagy in MSC biology and in heart failure, myocardial ischemia-reperfusion injury, cardiomyopathy, atherosclerosis, metabolic cardiovascular disease, and cardiovascular aging. Particular attention is given to the potential CSE/H2S-mitophagy-MSC axis and its possible value in cell preconditioning, pharmacological intervention, and targeted delivery. Current limitations, including difficulties in measuring mitophagy flux, disease-stage dependence, and the lack of a clearly defined therapeutic window, are also discussed.
文章引用:王海盟, 李龙, 朱小龙. 线粒体自噬在间充质干细胞干性维持及心血管疾病中的研究进展[J]. 临床医学进展, 2026, 16(8): 1131-1141. https://doi.org/10.12677/acm.2026.1682888

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