Sepsis-associated acute lung injury (SALI) is a common complication of sepsis, consisting of a dysfunctional host response to infection-mediated heterogenous complexes. SALI is reported in up to 50 % of patients with sepsis and causes poor outcomes. Despite high incidence, there is a lack of understanding in its pathogenesis and optimal treatment. A better understanding of the molecular mechanisms underlying SALI may help produce better therapeutics. The effects of altered cell-death mechanisms, such as non-apoptotic regulated cell death (RCD) (i.e., ferroptosis), on the development of SALI are beginning to be discovered, while targeting ferroptosis as a meaningful target in SALI is increasingly being recognized. Here, we outline how a susceptible lung alveoli may develop SALI. Then we discuss the general mechanisms underlying ferroptosis, and how it contributes to SALI. We then outline the chemical structures of the emerging agents or compounds that can protect against SALI by inhibiting ferroptosis, summarizing their potential pharmacological effects. Finally, we highlight key limitations and possible strategies to overcome them. This review suggests that a detailed mechanistic and biological understanding of ferroptosis can foster the development of pharmacological antagonists in the treatment of SALI.

中文翻译：

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靶向铁死亡为脓毒症相关急性肺损伤提供了治疗选择


脓毒症相关急性肺损伤 （SALI） 是脓毒症的一种常见并发症，包括宿主对感染介导的异质复合物的反应功能障碍。据报道，高达 50% 的脓毒症患者患有 SALI，并导致不良结局。尽管发病率高，但对其发病机制和最佳治疗方法缺乏了解。更好地了解 SALI 的分子机制可能有助于产生更好的治疗方法。改变的细胞死亡机制，例如非凋亡调节细胞死亡 （RCD）（即铁死亡）对 SALI 发展的影响开始被发现，而将铁死亡作为 SALI 中有意义的靶标越来越得到认可。在这里，我们概述了易感肺泡如何发展为 SALI。然后我们讨论了铁死亡的一般机制，以及它如何促进 SALI。然后，我们概述了可以通过抑制铁死亡来预防 SALI 的新兴试剂或化合物的化学结构，总结了它们的潜在药理作用。最后，我们重点介绍了关键限制和克服这些限制的可能策略。本综述表明，对铁死亡的详细机制和生物学理解可以促进治疗 SALI 的药物拮抗剂的发展。