线粒体功能障碍在慢性代谢性疾病中的研究进展

doi:10.12114/j.issn.1007-9572.2024.0677

中国全科医学 ›› 2026, Vol. 29 ›› Issue (18): 2577-2584.DOI: 10.12114/j.issn.1007-9572.2024.0677

• 综述与专论 • 上一篇

线粒体功能障碍在慢性代谢性疾病中的研究进展

简迎春¹, 曾永秦², 张海平¹, 王争地³, 安科¹, 严瑞¹^,²^,^*()

1．550004　贵州省贵阳市，贵州医科大学临床医学院
2．550004　贵州省贵阳市，贵州医科大学附属医院肾内科
3．550081　贵州省贵阳市，贵州医科大学附属金阳医院神经外科

收稿日期:2025-01-10 修回日期:2025-10-20 出版日期:2026-06-20 发布日期:2026-05-21
通讯作者: 严瑞
作者贡献：
简迎春负责研究命题的提出、论文撰写；曾永秦负责论文修改；张海平负责检索和整理；王争地、安科负责论文润色；严瑞负责文章的质量控制及监督管理。
基金资助:
国家自然科学基金资助项目(82260145); 贵州医科大学附属医院国家自然科学基金面上基金培养项目(gyfynsfc〔2024〕-03); 贵州省科学技术基金资助项目(黔科合基础-ZK〔2023〕一般378); 贵州省卫健委科技基金资助项目(gzwkj2023-026)

Recent Advances in Mitochondrial Dysfunction in Chronic Metabolic Diseases

JIAN Yingchun¹, ZENG Yongqin², ZHANG Haiping¹, WANG Zhengdi³, AN Ke¹, YAN Rui¹^,²^,^*()

1. School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China
2. Department of Nephrology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
3. Department of Neurosurgery, Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang 550081, China

Received:2025-01-10 Revised:2025-10-20 Published:2026-06-20 Online:2026-05-21
Contact: YAN Rui

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摘要/Abstract

摘要： 能量代谢失衡是糖尿病、动脉粥样硬化、神经退行性疾病、非酒精性脂肪肝等慢性代谢性疾病的共同特征，而线粒体功能受损被认为是其核心机制之一。线粒体功能障碍会导致氧化应激、代谢紊乱及炎症加剧，进而推动疾病进展。本综述系统探讨线粒体功能障碍在慢性代谢性疾病中的具体作用机制，并总结靶向线粒体的潜在治疗策略。通过检索筛选与线粒体功能障碍及慢性代谢性疾病相关的研究文献，重点分析线粒体结构、功能调控及其在疾病中的病理机制。线粒体功能障碍在不同疾病中表现出异常机制：糖尿病中活性氧过量生成与钙稳态失衡导致微血管病变；动脉粥样硬化中线粒体自噬受损加剧内皮损伤。此外，肥胖症和脂肪肝疾病中线粒体动力学异常显著促进代谢紊乱。靶向线粒体功能障碍的治疗策略（如抗氧化治疗、线粒体自噬调控及新兴的线粒体移植技术）展现出潜力，但仍需进一步临床验证。未来研究应关注线粒体精准干预与多机制协同治疗，为慢性代谢性疾病提供新思路。

关键词: 线粒体, 代谢性疾病, 动脉粥样硬化, 糖尿病, 阿尔茨海默病, 线粒体结构, 线粒体分布, 线粒体功能障碍

Abstract:

Imbalance in energy metabolism is a common feature of chronic metabolic diseases such as diabetes, atherosclerosis, neurodegenerative disorders, and non-alcoholic fatty liver disease, with mitochondrial dysfunction recognized as one of the core mechanisms. Abnormal mitochondrial function leads to oxidative stress, metabolic disturbances, and exacerbated inflammation, thereby driving disease progression. This review systematically explores the specific mechanisms of mitochondrial dysfunction in chronic metabolic diseases and summarizes potential mitochondria-targeted therapeutic strategies. By screening and analyzing relevant literature on mitochondrial dysfunction and chronic metabolic diseases, this study focuses on mitochondrial structure, functional regulation, and pathological mechanisms in disease contexts. Mitochondrial dysfunction manifests distinct mechanisms across different diseases: excessive reactive oxygen species production and calcium homeostasis imbalance in diabetes contribute to microvascular complications, while impaired mitophagy in atherosclerosis aggravates endothelial injury. Additionally, aberrant mitochondrial dynamics significantly promote metabolic dysregulation in obesity and fatty liver disease. Therapeutic strategies targeting mitochondrial dysfunction, such as antioxidant therapy, mitophagy modulation, and emerging mitochondrial transplantation techniques, show promise but require further clinical validation. Future research should emphasize precision mitochondrial interventions and synergistic multi-mechanism therapies to provide novel insights for managing chronic metabolic diseases.

Key words: Mitochondrium, Metabolic diseases, Atherosclerosis, Diabetes mellitus, Alzheimer's disease, Mitochondrial structure, Mitochondrial distribution, Mitochondrial dysfunction

中图分类号:

R 37

简迎春,曾永秦,张海平,等. 线粒体功能障碍在慢性代谢性疾病中的研究进展[J]. 中国全科医学, 2026, 29(18): 2577-2584. DOI: 10.12114/j.issn.1007-9572.2024.0677.
JIAN Yingchun,ZENG Yongqin,ZHANG Haiping, et al. Recent Advances in Mitochondrial Dysfunction in Chronic Metabolic Diseases[J]. Chinese General Practice, 2026, 29(18): 2577-2584. DOI: 10.12114/j.issn.1007-9572.2024.0677.

图/表 3

参考文献 72

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线粒体功能障碍类型	关联疾病及引用文献	关键机制
ROS过度生成	AD^[32]、HD^[32]、AS^[13]、NASH^[33]、DM^[34]、肥胖症^[3]	ROS过量导致氧化应激，损伤细胞和组织，促进炎症反应和疾病进展。
线粒体自噬受损	AD^[35]、AS^[13]、NASH^[33]、DM^[36]、线粒体肌病^[37]	受损线粒体无法被清除，导致ROS积累和能量代谢障碍，进一步加重细胞损伤
mtDNA突变或受损	AD^[38]、HD^[39]、AS^[13]、DM^[36]、线粒体肌病^[40]	mtDNA突变或损伤导致线粒体功能异常，影响能量生成和细胞稳态，促进疾病发展
生物发生异常	HD^[41]、肥胖症^[3]、线粒体肌病^[37]	线粒体生物发生受阻，导致线粒体数量减少和功能下降，影响能量代谢和组织功能
钙稳态失衡	HD^[41]、DM^[34]、肥胖症^[3]、线粒体肌病^[37]	线粒体钙摄取和释放失衡，导致细胞功能紊乱，影响能量代谢和细胞存活
能量失衡	HD^[39]、肥胖症^[42]	线粒体能量生成不足，导致细胞能量供应不足，影响组织功能和代谢平衡
线粒体裂变增加	AS^[13]、DM^[36]、肥胖症^[3]	线粒体过度裂变导致线粒体碎片化，功能受损，影响细胞能量代谢和组织功能

线粒体功能障碍类型	关联疾病及引用文献	关键机制
ROS过度生成	AD^[32]、HD^[32]、AS^[13]、NASH^[33]、DM^[34]、肥胖症^[3]	ROS过量导致氧化应激，损伤细胞和组织，促进炎症反应和疾病进展。
线粒体自噬受损	AD^[35]、AS^[13]、NASH^[33]、DM^[36]、线粒体肌病^[37]	受损线粒体无法被清除，导致ROS积累和能量代谢障碍，进一步加重细胞损伤
mtDNA突变或受损	AD^[38]、HD^[39]、AS^[13]、DM^[36]、线粒体肌病^[40]	mtDNA突变或损伤导致线粒体功能异常，影响能量生成和细胞稳态，促进疾病发展
生物发生异常	HD^[41]、肥胖症^[3]、线粒体肌病^[37]	线粒体生物发生受阻，导致线粒体数量减少和功能下降，影响能量代谢和组织功能
钙稳态失衡	HD^[41]、DM^[34]、肥胖症^[3]、线粒体肌病^[37]	线粒体钙摄取和释放失衡，导致细胞功能紊乱，影响能量代谢和细胞存活
能量失衡	HD^[39]、肥胖症^[42]	线粒体能量生成不足，导致细胞能量供应不足，影响组织功能和代谢平衡
线粒体裂变增加	AS^[13]、DM^[36]、肥胖症^[3]	线粒体过度裂变导致线粒体碎片化，功能受损，影响细胞能量代谢和组织功能

治疗策略	具体方法/药物	作用机制	适用疾病	参考文献
促进线粒体生物发生	间歇性禁食	激活线粒体生物发生相关信号通路，改善生物能量学	HD	[41]
	烟酰胺核苷、三萜类化合物	促进线粒体生物发生，改善线粒体功能	线粒体肌病	[56]
	利西那肽	促进线粒体生物发生，改善2型糖尿病患者的代谢	2型糖尿病	[57]
	二甲双胍	刺激线粒体生物发生和脂肪酸氧化，改善NAFLD	2型糖尿病、NAFLD	[33]
	SIRT1激活剂	促进线粒体生物发生，对抗肥胖相关的炎症反应	肥胖症	[58]
抗氧化应激	辅酶Q10	清除ROS，改善内皮功能和血脂水平，减轻糖尿病患者的高血糖症状	AS、DM	[13，59]
	肼屈嗪	预防氧化应激，减缓AD进展	AD	[62]
	N-乙酰半胱氨酸、维生素E	保护线粒体免受氧化损伤，改善HD症状	HD	[32]
调控线粒体动力学	半胱氨酸天冬氨酸蛋白水解酶1抑制剂	促进线粒体自噬，AS	AS	[67]
	亚精胺	诱导自噬，改善AD小鼠模型的疾病进展	AD	[6]
	尿石素A	增加线粒体自噬，减轻神经炎症，增强小胶质细胞吞噬作用	AD	[51]
	恩格列净	调节线粒体裂变和融合蛋白，使糖尿病大鼠心肌细胞ATP合成增加，同时降低ROS水平	DM	[19]
改善线粒体膜功能	ω-3脂肪酸	嵌入线粒体膜，增强膜流动性，减少炎症反应，改善认知功能	AD	[68]
改善线粒体膜功能	磷脂酰丝氨酸	稳定线粒体膜，增加流动性，保护神经	AD	[69]
其他新兴疗法	线粒体移植	用正常功能的线粒体替换受损线粒体，恢复ATP生成，减少ROS产生	糖尿病心肌缺血、精神疾病	[59，61]
	mtDNA编辑疗法	通过编辑mtDNA修复突变或缺失，治疗线粒体遗传疾病	线粒体遗传疾病	[13]
	mtDNA替代疗法	使用健康mtDNA替换缺陷mtDNA，预防线粒体母系遗传疾病	线粒体母系遗传疾病	[13]
	纳米技术	利用纳米载体靶向线粒体，实现药物高效输送	肿瘤、自身免疫性疾病	[71]
	嵌合抗原受体T细胞免疫疗法	识别和攻击线粒体功能障碍细胞，提供新的治疗策略	肿瘤、自身免疫性疾病	[72]

治疗策略	具体方法/药物	作用机制	适用疾病	参考文献
促进线粒体生物发生	间歇性禁食	激活线粒体生物发生相关信号通路，改善生物能量学	HD	[41]
	烟酰胺核苷、三萜类化合物	促进线粒体生物发生，改善线粒体功能	线粒体肌病	[56]
	利西那肽	促进线粒体生物发生，改善2型糖尿病患者的代谢	2型糖尿病	[57]
	二甲双胍	刺激线粒体生物发生和脂肪酸氧化，改善NAFLD	2型糖尿病、NAFLD	[33]
	SIRT1激活剂	促进线粒体生物发生，对抗肥胖相关的炎症反应	肥胖症	[58]
抗氧化应激	辅酶Q10	清除ROS，改善内皮功能和血脂水平，减轻糖尿病患者的高血糖症状	AS、DM	[13，59]
	肼屈嗪	预防氧化应激，减缓AD进展	AD	[62]
	N-乙酰半胱氨酸、维生素E	保护线粒体免受氧化损伤，改善HD症状	HD	[32]
调控线粒体动力学	半胱氨酸天冬氨酸蛋白水解酶1抑制剂	促进线粒体自噬，AS	AS	[67]
	亚精胺	诱导自噬，改善AD小鼠模型的疾病进展	AD	[6]
	尿石素A	增加线粒体自噬，减轻神经炎症，增强小胶质细胞吞噬作用	AD	[51]
	恩格列净	调节线粒体裂变和融合蛋白，使糖尿病大鼠心肌细胞ATP合成增加，同时降低ROS水平	DM	[19]
改善线粒体膜功能	ω-3脂肪酸	嵌入线粒体膜，增强膜流动性，减少炎症反应，改善认知功能	AD	[68]
改善线粒体膜功能	磷脂酰丝氨酸	稳定线粒体膜，增加流动性，保护神经	AD	[69]
其他新兴疗法	线粒体移植	用正常功能的线粒体替换受损线粒体，恢复ATP生成，减少ROS产生	糖尿病心肌缺血、精神疾病	[59，61]
	mtDNA编辑疗法	通过编辑mtDNA修复突变或缺失，治疗线粒体遗传疾病	线粒体遗传疾病	[13]
	mtDNA替代疗法	使用健康mtDNA替换缺陷mtDNA，预防线粒体母系遗传疾病	线粒体母系遗传疾病	[13]
	纳米技术	利用纳米载体靶向线粒体，实现药物高效输送	肿瘤、自身免疫性疾病	[71]
	嵌合抗原受体T细胞免疫疗法	识别和攻击线粒体功能障碍细胞，提供新的治疗策略	肿瘤、自身免疫性疾病	[72]

线粒体功能障碍在慢性代谢性疾病中的研究进展

Recent Advances in Mitochondrial Dysfunction in Chronic Metabolic Diseases

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