牙周炎中炎症–再生失偶联的线粒体基础及其 靶向治疗
Mitochondrial Basis of Resolution-Regeneration Uncoupling in Periodontitis and Its Targeted Therapy
摘要: 牙周炎是一种由失衡菌斑驱动、宿主免疫反应失调参与的慢性炎症性疾病，其治疗困难不仅在于炎症持续，更在于炎症控制后牙周组织难以实现有效重建。越来越多的证据提示，牙周炎中存在“炎症消退”与“再生启动”失偶联的困境，而线粒体功能障碍可能是连接两者的重要共同节点。在线粒体异常背景下，巨噬细胞表现为促炎偏向持续化、炎症消退受阻及促破骨活性增强；同时再生相关细胞表现出成骨潜能下降及免疫表型重塑。此外，线粒体功能障碍还可通过改变细胞的代谢适应性、影响旁分泌信号传导等影响细胞间互作，进一步促进细胞间的病理串扰。基于此，线粒体靶向治疗正由单纯的抑炎或促再生，转向从上游的线粒体这一信号枢纽协调炎症消退与组织修复的启动。本文以巨噬细胞–干细胞轴为主线，综述线粒体功能障碍在牙周炎“炎症–再生失偶联”中的作用机制，并总结线粒体靶向治疗的主要策略、研究进展及当前局限，以期为牙周炎骨免疫调控与再生治疗提供综合性视角。
Abstract: Periodontitis is a chronic inflammatory disease driven by dysbiotic plaque and dysregulated host immunity. Its therapeutic challenge lies not only in persistent inflammation, but also in the limited capacity for effective periodontal reconstruction after inflammation is controlled. Increasing evidence suggests that periodontitis is characterized by uncoupling of resolution-regeneration, and mitochondrial dysfunction may serve as a key shared node linking these processes. Under mitochondrial stress, macrophages exhibit sustained pro-inflammatory polarization, impaired inflammatory resolution, and enhanced osteoclastogenic activity, whereas regenerative cells show reduced osteogenic potential and reshaped immunophenotypes. In addition, mitochondrial dysfunction may further sustain pathological crosstalk by altering metabolic adaptation, paracrine signaling, and intercellular interactions. Consequently, mitochondria-targeted interventions are shifting from simple anti-inflammatory or pro-regenerative approaches toward coordinated regulation of inflammatory maintenance and tissue repair at an upstream mitochondrial level. Focusing on the macrophage-stem cell axis, this review summarizes the mechanisms by which mitochondrial dysfunction contributes to the uncoupling of resolution-regeneration in periodontitis, and discusses the major mitochondria-targeted therapeutic strategies, recent advances, and current limitations, aiming to provide a comprehensive perspective for osteoimmunomodulation and regenerative therapy in periodontitis.
文章引用：严彤, 张曦木. 牙周炎中炎症–再生失偶联的线粒体基础及其 靶向治疗[J]. 临床医学进展, 2026, 16(4): 4121-4128. https://doi.org/10.12677/acm.2026.1641680

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