心肌缺血再灌注损伤中的恶性循环:铁死亡与炎症的互作机制

The vicious cycle:ferroptosis-inflammation crosstalk in myocardial ischemia/reperfusion injury

摘要:

心肌缺血再灌注损伤(MIRI)涉及多种细胞死亡机制,其中铁死亡与炎症已被证实是驱动MIRI进展的两个关键因素。目前,在MIRI中,关于铁死亡或炎症的单一机制研究相对较完善,但在损伤后期,铁死亡与炎症可形成正反馈循环,进一步加重心肌损伤,且二者间交互作用的具体分子机制及动态调控网络尚未明确。文章系统梳理了铁死亡与炎症在MIRI中的独立作用路径,同时整合了二者相互调控的新证据,并提出了靶向铁死亡-炎症正反馈循环的潜在治疗策略。将有助于开发新的治疗干预手段,为临床治疗MIRI提供理论依据。

Abstract:

Myocardial ischemia/reperfusion injury (MIRI) involves multiple cell death mechanisms, among which ferroptosis and inflammation have been identified as two key drivers of MIRI progression. Although the independent roles of ferroptosis or inflammation in MIRI have been relatively well studied, emerging evidence indicates that in the later stages of injury, ferroptosis and inflammation can form a positive feedback loop, further exacerbating myocardial damage. However, the precise molecular interactions and dynamic regulatory networks between ferroptosis and inflammation in MIRI remain unclear. This review systematically outlines the distinct pathways through which ferroptosis and inflammation contribute to MIRI, integrates recent findings on their mutual regulation, and proposes potential therapeutic strategies targeting the ferroptosis-inflammation positive feedback loop. By elucidating these mechanisms, this review aims to facilitate the development of novel therapeutic interventions and provide a theoretical foundation for the clinical management of MIRI.