Vázquez-Galán Yarielis Ivette, Guzmán-Silahua Sandra, Trujillo-Rangel Walter Ángel, Rodríguez-Lara Simón Quetzalcoatl
School of Medicine International Program, Universidad Autónoma de Guadalajara, Av. Patria 1201, Zapopan 45129, Jalisco, Mexico.
Unidad de Investigación Epidemiológica y en Servicios de Salud, Centro Médico Nacional de Occidente Órgano de Operación Administrativa Desconcentrada Jalisco, Instituto Mexicano del Seguro Social, Guadalajara 44329, Jalisco, Mexico.
Cells. 2025 May 30;14(11):808. doi: 10.3390/cells14110808.
Shock is a life-threatening condition characterized by inadequate tissue perfusion leading to systemic hypoxia and metabolic failure. Ischemia/reperfusion (I/R) injury exacerbates shock progression through oxidative stress and immune dysregulation, contributing to multi-organ dysfunction. This narrative review synthesizes current evidence on the interplay between I/R injury, oxidative stress, and immune modulation in shock states. We analyze the classification of shock, its progression, and the molecular pathways involved in ischemic adaptation, inflammatory responses, and oxidative injury. Shock pathophysiology is driven by systemic ischemia, triggering adaptive responses such as hypoxia-inducible factor (HIF) signaling and metabolic reprogramming. However, prolonged hypoxia leads to mitochondrial dysfunction, increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, and immune activation. The transition from systemic inflammatory response syndrome (SIRS) to compensatory anti-inflammatory response syndrome (CARS) contributes to immune imbalance, further aggravating tissue damage. Dysregulated immune checkpoint pathways, including CTLA-4 and PD-1, fail to suppress excessive inflammation, exacerbating oxidative injury and immune exhaustion. The intricate relationship between oxidative stress, ischemia/reperfusion injury, and immune dysregulation in shock states highlights potential therapeutic targets. Strategies aimed at modulating redox homeostasis, controlling immune responses, and mitigating I/R damage may improve patient outcomes. Future research should focus on novel interventions that restore immune balance while preventing excessive oxidative injury.
休克是一种危及生命的状况，其特征是组织灌注不足，导致全身缺氧和代谢衰竭。缺血/再灌注（I/R）损伤通过氧化应激和免疫失调加剧休克进展，导致多器官功能障碍。这篇叙述性综述综合了关于休克状态下I/R损伤、氧化应激和免疫调节之间相互作用的现有证据。我们分析了休克的分类、进展以及缺血适应、炎症反应和氧化损伤所涉及的分子途径。休克病理生理学由全身缺血驱动，引发适应性反应，如缺氧诱导因子（HIF）信号传导和代谢重编程。然而，长时间缺氧会导致线粒体功能障碍、活性氧（ROS）和活性氮（RNS）生成增加以及免疫激活。从全身炎症反应综合征（SIRS）向代偿性抗炎反应综合征（CARS）的转变导致免疫失衡，进一步加重组织损伤。包括细胞毒性T淋巴细胞相关抗原4（CTLA-4）和程序性死亡蛋白1（PD-1）在内的免疫检查点途径失调，无法抑制过度炎症，加剧氧化损伤和免疫耗竭。休克状态下氧化应激、缺血/再灌注损伤和免疫失调之间的复杂关系突出了潜在的治疗靶点。旨在调节氧化还原稳态、控制免疫反应和减轻I/R损伤的策略可能会改善患者预后。未来的研究应侧重于恢复免疫平衡同时防止过度氧化损伤的新型干预措施。
