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线粒体动力学在糖尿病心肌病中的作用及调节机制

岳欢^1,2, 德德玛³, 丁铭格³, 付锋^2,*

¹西北大学生命科学学院，西安 710069；²空军军医大学生理与病理生理学教研室，西安 710032；³西安交通大学第二附属医院老年心血管科，西安 710004

摘要

心血管并发症是糖尿病患者死亡的首要原因。其中，糖尿病心肌病是排除了高血压、冠心病所致的心肌损伤后的一类特异性心肌病，其特征在于心肌细胞的代谢异常和心脏功能的逐渐衰退，临床表现为早期心肌舒张功能受损，晚期心肌收缩功能受损，最终发展为心力衰竭。线粒体是心肌细胞内提供能量的主要细胞器，线粒体动力学是指线粒体进行融合和分裂的动态过程，是线粒体质量控制的重要途径，线粒体动力学在维持线粒体稳态与心脏功能中起着至关重要的作用。调节线粒体分裂的蛋白主要是Drp1及其受体Fis1、MFF、MiD49和MiD51，执行线粒体外膜融合的蛋白为Mfn1/2，内膜融合蛋白为Opa1。本文综述了近期在糖尿病心肌病线粒体动力学方面的系列研究成果：1型与2型糖尿病心肌病的线粒体动力学失衡均表现为分裂增加与融合受阻，前者的分子机制主要是Drp1上调与Opa1下调，后者的分子机制主要为Drp1上调与Mfn1/2下调，线粒体分裂增加和融合受阻可导致线粒体功能障碍，促进糖尿病心肌病的发生、发展。中药单体安石榴苷、丹皮酚和内源性物质褪黑素等活性成分可通过抑制线粒体分裂或促进线粒体融合，改善线粒体功能，减轻糖尿病心肌病症状。本文有助于深入认识线粒体动力学在糖尿病心肌病中的作用及机制，为糖尿病心肌病患者提供基于线粒体动力学的新治疗方法和干预策略。

关键词： 糖尿病心肌病; 线粒体动力学; 线粒体融合; 线粒体分裂; 线粒体功能; 转录; 翻译后修饰

Role of mitochondrial dynamics in diabetic cardiomyopathy and regulatory mechanisms

YUE Huan^1,2, DE De-Ma³, DING Ming-Ge³, FU Feng^2,*

¹School of Life Sciences, Northwestern University, Xi’an 710069, China；²Department of Physiology and Pathophysiology, Air Force Medical University, Xi’an 710032, China；³Department of Geriatric Cardiology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China

Abstract

Cardiovascular complications are the leading cause of death in diabetic patients. Among them, diabetic cardiomyopathy (DCM) is a type of specific cardiomyopathy excluding myocardial damage caused by hypertension and coronary heart disease. It is characterized by abnormal metabolism of cardiomyocytes and gradual decline of cardiac function. The clinical manifestations of DCM are impaired diastolic function in early stage and impaired systolic function in late stage. Eventually it developed into heart failure. Mitochondria are the main organelles that provide energy in cardiomyocytes. Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission, which is an important approach for mitochondrial quality control. Mitochondrial dynamics plays a crucial role in maintaining mitochondrial homeostasis and cardiac function. The proteins that regulate mitochondrial fission are mainly Drp1 and its receptors, Fis1, MFF, MiD49 and MiD51. The protein that performs mitochondrial outer membrane fusion is Mfn1/2, and the inner membrane fusion protein is Opa1. This paper reviews recent progress on mitochondrial dynamics in DCM. The main contents are as follows: mitochondrial dynamics imbalance in both type 1 and 2 DCM is manifested as increased fission and inhibited fusion. The molecular mechanism of the former is mainly associated with up-regulated Drp1 and down-regulated Opa1, while the molecular mechanism of the latter is mainly associated with up-regulated Drp1 and down-regulated Mfn1/2. Increased mitochondrial fission and inhibited fusion can lead to mitochondrial dysfunction and promote the development of DCM. The active ingredients of the traditional Chinese medicine such as punicalagin, paeonol and endogenous substance melatonin can improve mitochondrial function and alleviate the symptoms of DCM by inhibiting mitochondrial fission or promoting mitochondrial fusion. This article is helpful to further understand the role and mechanism of mitochondrial dynamics in DCM, and provide new treatment methods and intervention strategies for clinical DCM patients based on mitochondrial dynamics.

Key words: diabetic cardiomyopathy; mitochondrial dynamics; mitochondrial fusion; mitochondrial fission; mitochondrial function; transcription; post-translational modification

收稿日期：　　录用日期：

通讯作者：付锋　　E-mail: fufeng048@126.com

DOI: 10.13294/j.aps.2024.0012

引用本文：

岳欢, 德德玛, 丁铭格, 付锋. 线粒体动力学在糖尿病心肌病中的作用及调节机制[J]. 生理学报 2024; 76 (1): 128-136.

YUE Huan, DE De-Ma, DING Ming-Ge, FU Feng. Role of mitochondrial dynamics in diabetic cardiomyopathy and regulatory mechanisms. Acta Physiol Sin 2024; 76 (1): 128-136 (in Chinese with English abstract).