NAD依赖性蛋白脱乙酰酶Sirtuin-3对糖尿病心肌病影响及机制研究进展
Advanced Research on the Effects and Mechanisms of NAD-Dependent Protein Deacetylase Sirtuin-3 in Diabetic Cardiomyopathy
摘要: 糖尿病心肌病(Diabetic Cardiomyopathy, DCM)是糖尿病引发的主要累及心肌，独立于冠状动脉疾病、瓣膜病变及其他常规心血管危险因素(如高血压、血脂异常)的严重心脏并发症，表现为心肌功能障碍。其主要病理特征包括心肌细胞肥大、心肌纤维化及心室收缩/舒张功能受损，最终可导致广泛心肌损伤与坏死，现已成为全球心力衰竭的重要诱因。线粒体脱乙酰酶Sirtuin-3 (SIRT3)是一种NAD⁺依赖性蛋白去乙酰化酶，在心脏等代谢活跃组织高表达。SIRT3通过调控脂肪酸氧化、三羧酸循环(TCA)、氧化磷酸化(OXPHOS)、活性氧(ROS)平衡及蛋白质乙酰化修饰水平，维持线粒体功能与代谢稳态。研究表明，SIRT3功能异常与糖尿病心肌病、心肌肥大、动脉粥样硬化等多种心血管疾病的发生发展密切相关。本综述系统探讨了SIRT3在糖尿病心肌病发病中的关键作用及相关分子机制，旨在为深入理解糖尿病心肌病病理生理过程及寻找潜在防治靶点提供科学依据。
Abstract: Diabetic Cardiomyopathy (DCM) is a severe diabetic complication primarily affecting cardiac muscle, characterized by myocardial dysfunction independent of coronary artery disease, valvulopathies, and other conventional cardiovascular risk factors (e.g., hypertension, dyslipidemia). Its core pathological features encompass cardiomyocyte hypertrophy, myocardial fibrosis, and impaired ventricular systolic/diastolic function, ultimately leading to extensive myocardial damage and necrosis. DCM has emerged as a significant contributor to global heart failure. Sirtuin-3 (SIRT3), a mitochondrial NAD⁺-dependent protein deacetylase, is highly expressed in metabolically active tissues including the heart. SIRT3 maintains mitochondrial function and metabolic homeostasis by regulating fatty acid oxidation, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS) balance, and protein acetylation modifications. Studies demonstrate that SIRT3 dysfunction is critically implicated in the pathogenesis of various cardiovascular diseases, including DCM, cardiac hypertrophy, and atherosclerosis. This review systematically explores the pivotal role and molecular mechanisms of SIRT3 in DCM pathogenesis, aiming to advance the understanding of DCM pathophysiology and identify potential therapeutic targets.
文章引用：孙文月. NAD依赖性蛋白脱乙酰酶Sirtuin-3对糖尿病心肌病影响及机制研究进展[J]. 临床医学进展, 2025, 15(11): 1491-1497. https://doi.org/10.12677/acm.2025.15113247

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