基于AMPK/mTOR信号通路介导自噬探讨中医药治疗心力衰竭的机制研究进展

Traditional Chinese Medicine Treats Heart Failure by Regulating Autophagy via AMPK/mTOR Signaling Pathway： A Review

摘要:

心力衰竭（HF）是一种由心脏功能障碍引起心室泵血功能受损的一组综合征，严重影响患者的健康和生活质量。HF的发病机制复杂，包括心肌收缩力减退、心肌细胞纤维化和心室重构等多个方面，并与神经内分泌调节、炎症反应及心肌细胞自噬等多种因素有关。自噬是一种细胞通过自我降解的方式，以维持机体稳态的重要调节机制。在HF的进程中，适度的自噬能够清除老化和受损的心肌细胞、维持心肌能量代谢平衡，而异常的自噬则可能会导致心肌细胞的功能减退和病理性改变。腺苷酸活化蛋白激酶（AMPK）/哺乳动物雷帕霉素哺乳靶蛋白（mTOR）则是调控自噬的经典通路之一，可以通过调控AMPK/mTOR信号通路介导心肌细胞自噬过程，起到保护心脏功能，延缓HF进程的作用。中医药在历史长河中不断发展和创新，有着独特的理论体系，并在与现代医学的交汇下表现出卓越的疗效与广泛的应用前景。临床实践中，中医药在治疗心血管疾病方面有着丰富经验，大量国内外研究表明，许多中药有效成分、中药复方及中成药可以通过调节AMPK/mTOR信号通路介导自噬以达到治疗HF的目的。笔者从AMPK/mTOR信号通路介导自噬的作用机制出发，阐释该机制在治疗HF过程中的关键作用，并基于中医相关理论探讨对自噬、AMPK/mTOR信号通路和HF的理解，同时对中医药通过AMPK/mTOR通路调控自噬治疗HF进行了综述，以期深入挖掘中医药在心血管疾病治疗中的潜力，为后续实验研究提供理论支持，并在临床上展现中医优势，实现更加精准化的治疗。

Abstract:

Heart failure （HF） is a group of syndromes caused by cardiac dysfunction with impaired ventricular pumping， seriously affecting patients' health and quality of life. The pathogenesis of HF is complex， including myocardial contractility decline， myocardial fibrosis， and ventricular remodeling， and it is related to neuroendocrine regulation， inflammation， and cardiomyocyte autophagy. Autophagy is a key regulatory mechanism by which cells degrade themselves to maintain body homeostasis. In the process of HF， moderate autophagy can remove aging and damaged cardiomyocytes and maintain the balance of myocardial energy metabolism， while abnormal autophagy may lead to functional decline and pathological changes of cardiomyocytes. The adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway is one of the classical pathways regulating autophagy. This pathway can mediate the autophagy of cardiomyocytes and play a role in protecting the cardiac function and delaying HF progression. Traditional Chinese medicine （TCM） with a long history has a unique theoretical system and shows satisfactory therapeutic effects and wide application prospects amid the integration with modern medicine. The clinical practice of TCM has accumulated rich experience in the treatment of cardiovascular diseases. A large number of studies have shown that the active components and compound prescriptions of TCM and Chinese patent medicines can mediate autophagy by regulating the AMPK/mTOR signaling pathway to treat HF. This article explains the role of AMPK/mTOR signaling pathway-mediated autophagy in the treatment of HF， introduces the understanding of autophagy， AMPK/mTOR signaling pathway， and HF based on TCM theories， and reviews the research progress in the regulation of autophagy by TCM in the treatment of HF via the AMPK/mTOR pathway. This review is expected to tap the potential of TCM in the treatment of cardiovascular diseases， provide theoretical support for subsequent experimental studies， and demonstrate the advantages of TCM in clinical practice to achieve more accurate treatment.