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心脏β-肾上腺素受体调控线粒体功能在心力衰竭中的研究进展

刘爱明^1,*, 徐文丽², 肖晗¹, 董尔丹¹

¹北京大学第三医院心内科、血管医学研究所；血管稳态与重构全国重点实验室(北京大学)；北京大学临床医学高等研究院；国家卫生健康委心血管分子生物学与调节肽重点实验室；心血管受体研究北京市重点实验室，北京 100191；²康复大学青岛医院(青岛市市立医院)心肺康复研究中心；康复大学生命科学与健康学院，青岛 266113

摘要

β-肾上腺素受体(β-adrenergic receptor, β-AR)的异常激活以及线粒体功能障碍是促进心力衰竭发生、发展的重要病理因素。心力衰竭时，β-AR及下游信号通路的过度激活介导心肌细胞氧化应激、钙超载、代谢异常等关键病理过程，进而引起心脏炎症、心肌细胞凋亡及坏死。线粒体作为心肌细胞能量及物质代谢的核心细胞器，其数目及功能的稳态亦与细胞内钙离子水平、氧化还原平衡及信号转导密切相关。适度激活的β-AR信号通路有利于线粒体稳态的维持，介导心肌细胞正常生理功能的发挥。然而，心力衰竭时异常激活的β-AR及下游信号通路通过多种途径介导线粒体功能障碍。因此，本综述阐述β-AR及下游信号通路对线粒体的调控，以期揭示交感应激下线粒体异常所介导的氧化应激、细胞凋亡及坏死、代谢紊乱在心力衰竭中的作用，为心力衰竭的防治提供新的思路和治疗靶点。

关键词： β-肾上腺素受体; 线粒体稳态; 氧化应激; 凋亡; 坏死; 代谢

Cardiac β-adrenergic receptor regulation of mitochondrial function in heart failure

LIU Ai-Ming^1,*, XU Wen-Li², XIAO Han¹, DONG Er-Dan¹

¹Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University; Institute of Advanced Clinical Medicine, Peking University; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Beijing Key Laboratory of ardiovascular Receptors Research, Beijing 100191, China；²Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital); School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China

Abstract

Heart failure is characterized by abnormal β-adrenergic receptor (β-AR) activation and mitochondrial dysfunction. In heart failure, overactivation of β-AR mediates key pathological processes in cardiomyocytes, including oxidative stress, calcium overload and metabolic abnormalities, which subsequently lead to inflammation, myocardial apoptosis and necrosis. Mitochondria are the core organelles for energy metabolism, and also play a vital role in calcium homeostasis, redox balance and signaling transduction. Moderate β-AR activation is conducive to maintaining mitochondrial homeostasis and physiological cardiomyocyte function. However, β -AR overactivation in heart failure disrupts mitochondrial function through multiple mechanisms. Therefore, our review aims to elucidate how β -AR regulates mitochondrial function, particularly under sympathetic stress, impacting oxidative stress, apoptosis, necrosis, and metabolic imbalance. By describing these mechanisms, we seek to propose new insights and therapeutic targets for the prevention and treatment of heart failure.

Key words: β-adrenergic receptor; mitochondrial homeostasis; oxidative stress; apoptosis; necrosis; metabolism

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引用本文：

刘爱明, 徐文丽, 肖晗, 董尔丹. 心脏β-肾上腺素受体调控线粒体功能在心力衰竭中的研究进展[J]. 生理学报 2024; 76 (6): 865-880.

LIU Ai-Ming, XU Wen-Li, XIAO Han, DONG Er-Dan. Cardiac β-adrenergic receptor regulation of mitochondrial function in heart failure. Acta Physiol Sin 2024; 76 (6): 865-880 (in Chinese with English abstract).