自噬在椎间盘退变中的研究进展

Research Progress of Autophagy in Intervertebral Disc Degeneration

摘要: 椎间盘退变(Intervertebral disc degeneration, IVDD)是导致LBP的病理基础，对全球健康及经济造成了极大的危害。椎间盘内部微环境具有无血管、低氧、高渗和营养匮乏等特征。髓核细胞(Nucleus pulposus cells, NPCs)作为维持椎间盘细胞外基质(Extracellular matrix, ECM)稳态的核心效应细胞，在退变过程中常发生凋亡、衰老等功能障碍。自噬(Autophagy)作为一种高度保守的细胞内降解及回收机制，在清除受损细胞器、错误折叠蛋白以及维持细胞内环境稳态中发挥重要作用。近年来，越来越多的研究表明，自噬在IVDD中扮演着“双刃剑”的角色。适度的自噬激活可促进髓核细胞抵御氧化应激、炎症反应等损伤，进而延缓NPCs衰老与ECM降解；然而，过度自噬或自噬流(Autophagic flux)受阻则可能诱发自噬性细胞死亡，进而加速IVDD的发生发展。本文系统综述了自噬在IVDD发病机制中的双重作用，重点探讨微环境的改变对自噬的调控作用，并深入分析了相关信号通路在其中的调控机制。此外，本文还总结了靶向自噬治疗IVDD的相关策略，旨在为IVDD的临床防治提供新的理论依据和潜在的治疗靶点。

Abstract: Intervertebral disc degeneration (IVDD) is the pathological basis of low back pain, posing a significant burden on global health and the economy. The internal microenvironment of the intervertebral disc is characterized by avascularity, hypoxia, hyperosmolarity, and nutrient deprivation. Nucleus pulposus cells (NPCs), serving as the core effector cells that maintain the homeostasis of the extracellular matrix (ECM) within the intervertebral disc, frequently undergo dysfunctions such as apoptosis and senescence during the degeneration process. Autophagy, a highly conserved intracellular degradation and recycling mechanism, plays a crucial role in clearing damaged organelles and misfolded proteins, as well as maintaining intracellular homeostasis. In recent years, an increasing number of studies have indicated that autophagy plays a "double-edged sword" role in IVDD. Moderate activation of autophagy can promote the resistance of NPCs to damages such as oxidative stress and inflammatory responses, thereby delaying NPCs senescence and ECM degradation. However, excessive autophagy or impaired autophagic flux may induce autophagic cell death, consequently accelerating the onset and progression of IVDD. This article systematically reviews the dual role of autophagy in the pathogenesis of IVDD, with a focus on exploring the regulatory effects of microenvironmental changes on autophagy, and provides an in-depth analysis of the underlying regulatory mechanisms of related signaling pathways. Furthermore, this article summarizes the relevant strategies of targeting autophagy for IVDD treatment, aiming to provide new theoretical rationales and potential therapeutic targets for the clinical prevention and management of IVDD.