Department of Emergency, The First Hospital of China Medical University, Shenyang, China.
Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, China.
Front Immunol. 2024 Apr 16;15:1394925. doi: 10.3389/fimmu.2024.1394925. eCollection 2024.
Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.
脓毒症是一种危及生命的器官功能障碍，由宿主对感染的功能失调反应引起。免疫系统的异常激活和能量代谢紊乱在脓毒症的发生发展中起着关键作用。近年来，发现 Sirtuins（SIRTs）家族在脓毒症的发病机制中起着重要作用。SIRTs 作为一类组蛋白去乙酰化酶（HDACs），广泛参与细胞炎症调节、能量代谢和氧化应激。SIRTs 对免疫细胞的作用主要体现在对炎症途径的调节。这种调节有助于平衡炎症反应，可能减轻脓毒症中细胞损伤和器官功能障碍。在能量代谢方面，SIRTs 通过调节细胞代谢、改善线粒体功能、增加能量产生和维持细胞能量平衡来发挥免疫表型转化的作用。SIRTs 还调节活性氧物质（ROS）的产生，通过激活抗氧化防御途径和维持氧化剂和还原剂之间的平衡来保护细胞免受氧化应激损伤。目前的研究表明，几种潜在的药物，如白藜芦醇和褪黑素，可以增强 SIRT 的活性。它有助于减轻炎症反应、改善能量代谢和减少氧化应激，为脓毒症的治疗展示了潜在的临床应用前景。本综述重点关注 SIRT 对免疫细胞炎症反应、能量代谢和氧化应激的调节作用，以及其对脓毒症多器官功能障碍的重要影响，并通过涉及 SIRTs 的途径讨论和总结了相关药物和化合物对减轻脓毒症多器官损伤的作用。SIRTs 可能成为治疗脓毒症及其导致的器官功能障碍的新靶点，为治疗这种危及生命的疾病提供了新的思路和可能性。
