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[巨噬细胞在脓毒症性心肌病发病机制中的作用]

[Role of macrophages in the pathogenesis of septic cardiomyopathy].

作者信息

Zhang Linke, Zhao Zhiling, Li Tingcui, Li Wen, Leng Yuxin, Ge Qinggang

机构信息

Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China. Corresponding author: Ge Qinggang, Email:

出版信息

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2025 Mar;37(3):305-309. doi: 10.3760/cma.j.cn121430-20240925-00797.

Abstract

Sepsis is a life-threatening organ dysfunction caused by the body's dysregulated response to infection. Reversible myocardial dysfunction caused by sepsis is known as septic cardiomyopathy. A thorough understanding of the pathogenesis of septic cardiomyopathy is crucial for early intervention to prevent its progression and improve the success rate of sepsis treatment. At present, the research on the pathogenesis of septic cardiomyopathy mainly focuses on two aspects: the systemic neuroimmune mechanism and the local changes of cardiomyocytes. The former mainly includes the autonomic nervous dysfunction mainly caused by sympathetic overactivation and the inflammatory storm induced by immune response disorder. The latter covers the dysregulation of calcium homeostasis, mitochondrial dysfunction and energy metabolism disorder of cardiomyocytes. Immune dysfunction is one of the key factors that cause the poor prognosis of patients with septic cardiomyopathy. Macrophages are sentinel cells of the body's innate immunity. Cardiac macrophages have been confirmed to be one of the most heterogeneous immune cells in the heart. According to their origin and differentiation, they can be divided into bone marrow-derived tissue infiltrating macrophages and cardiac resident macrophages, which have roles of polarization, phagocytosis, regulation of inflammatory response, and participate in innate and adaptive immunity. In the occurrence and development of septic cardiomyopathy, cardiac macrophages recruited from the blood participate in balancing the inflammation and repair of myocardial tissue through the conversion of pro-inflammatory phenotype and anti-inflammatory phenotype. Cardiac resident macrophages mediate immune phagocytosis to maintain the local homeostasis of cardiomyocytes, and the glycometabolic reprogramming of macrophages regulates the release of inflammatory factors, while macrophage metabolic reprogramming regulates the release of inflammatory factors. A deeper understanding of the biological behavior of macrophages, and regulating the polarization, metabolism and phagocytosis of cardiac macrophages, could serve as new target for the prevention and treatment of septic cardiomyopathy. Therefore, this article reviews the key pathogenesis of septic cardiomyopathy and the role of macrophages of different origins and differentiation, revealing the possibility of developing new strategies for the prevention and treatment of septic cardiomyopathy.

摘要

脓毒症是由机体对感染的反应失调引起的危及生命的器官功能障碍。由脓毒症引起的可逆性心肌功能障碍称为脓毒症性心肌病。深入了解脓毒症性心肌病的发病机制对于早期干预以防止其进展并提高脓毒症治疗成功率至关重要。目前,关于脓毒症性心肌病发病机制的研究主要集中在两个方面:全身神经免疫机制和心肌细胞的局部变化。前者主要包括主要由交感神经过度激活引起的自主神经功能障碍以及免疫反应紊乱诱导的炎症风暴。后者涵盖心肌细胞钙稳态失调、线粒体功能障碍和能量代谢紊乱。免疫功能障碍是导致脓毒症性心肌病患者预后不良的关键因素之一。巨噬细胞是机体固有免疫的哨兵细胞。心脏巨噬细胞已被证实是心脏中最具异质性的免疫细胞之一。根据其起源和分化,它们可分为骨髓来源的组织浸润巨噬细胞和心脏驻留巨噬细胞,它们具有极化、吞噬、调节炎症反应的作用,并参与固有免疫和适应性免疫。在脓毒症性心肌病的发生发展过程中,从血液中募集而来的心脏巨噬细胞通过促炎表型和抗炎表型的转换参与平衡心肌组织的炎症和修复。心脏驻留巨噬细胞介导免疫吞噬以维持心肌细胞的局部稳态,而巨噬细胞的糖代谢重编程调节炎症因子的释放,同时巨噬细胞代谢重编程调节炎症因子的释放。更深入地了解巨噬细胞的生物学行为,并调节心脏巨噬细胞的极化、代谢和吞噬作用,可以作为预防和治疗脓毒症性心肌病的新靶点。因此,本文综述了脓毒症性心肌病的关键发病机制以及不同起源和分化的巨噬细胞的作用,揭示了开发脓毒症性心肌病预防和治疗新策略的可能性。

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