Department of Emergency Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
Biomed Pharmacother. 2024 Nov;180:117513. doi: 10.1016/j.biopha.2024.117513. Epub 2024 Sep 27.
Cardiac arrest (CA) is a significant challenge for emergency physicians worldwide and leads to increased morbidity and mortality rates. The poor prognosis of CA primarily stems from the complexity and irreversibility of cerebral ischemia-reperfusion injury (CIRI). Ferroptosis, a form of programmed cell death characterized by iron overload and lipid peroxidation, plays a crucial role in the progression and treatment of CIRI. In this review, we highlight the mechanisms of ferroptosis within the context of CIRI, focusing on its role as a key contributor to neuronal damage and dysfunction post-CA. We explore the crucial involvement of the nuclear factor erythroid 2-related factor (Nrf2)-mediated signaling pathway in modulating ferroptosis-associated processes during CIRI. Through comprehensive analysis of the regulatory role of Nrf2 in the cellular responses to oxidative stress, we highlight its potential as a therapeutic target for mitigating ferroptotic cell death and improving the neurological prognosis of patients experiencing CA. Furthermore, we discuss interventions targeting the Kelch-like ECH-associated protein 1/Nrf2/antioxidant response element pathway, including the use of traditional Chinese medicine and Western medicine, which demonstrate potential for attenuating ferroptosis and preserving neuronal function in CIRI. Owing to the limitations in the safety, specificity, and effectiveness of Nrf2-targeted drugs, as well as the technical difficulties and ethical constraints in obtaining the results related to the brain pathological examination of patients, most of the studies focusing on Nrf2-related regulation of ferroptosis in CIRI are still in the basic research stage. Overall, this review aims to provide a comprehensive understanding of the mechanisms underlying ferroptosis in CIRI, offering insights into novel therapeutics aimed at enhancing the clinical outcomes of patients with CA.
心脏骤停 (CA) 是全球急诊医生面临的重大挑战，导致发病率和死亡率上升。CA 预后不良主要源于脑缺血再灌注损伤 (CIRI) 的复杂性和不可逆性。铁死亡是一种以铁过载和脂质过氧化为特征的程序性细胞死亡形式，在 CIRI 的进展和治疗中起着至关重要的作用。在本综述中，我们重点介绍了 CIRI 中铁死亡的机制，特别强调了它在 CA 后神经元损伤和功能障碍中的关键作用。我们探讨了核因子红细胞 2 相关因子 (Nrf2) 介导的信号通路在调节 CIRI 中铁死亡相关过程中的关键作用。通过综合分析 Nrf2 在细胞对氧化应激反应中的调节作用，我们强调了它作为减轻铁死亡细胞死亡和改善 CA 患者神经预后的治疗靶点的潜力。此外，我们还讨论了针对 Kelch 样 ECH 相关蛋白 1/Nrf2/抗氧化反应元件通路的干预措施，包括中药和西药的应用，这些措施显示出在 CIRI 中减轻铁死亡和保护神经元功能的潜力。由于 Nrf2 靶向药物的安全性、特异性和有效性的限制，以及获得与患者脑病理检查相关结果的技术困难和伦理限制，大多数关于 CIRI 中 Nrf2 相关铁死亡调节的研究仍处于基础研究阶段。总的来说，本综述旨在全面了解 CIRI 中铁死亡的机制，为增强 CA 患者的临床转归提供新的治疗策略。
