Research Progress of Ferroptosis in Acute Lung Injury

doi:10.12114/j.issn.1007-9572.2022.0186

Abstract

Abstract:

Ferroptosis, a novel programmed cell death characterized by intracellular accumulation of lipid peroxides, has played an important role in a wide range of diseases. Acute lung injury is a critical illness caused by several reasons, and the mortality rate is high. With increasing research on the mechanism of acute lung injury, more evidence has shown that ferroptosis played an important role in the pathogenesis of acute lung injury. In this paper, we sorted the previous studies related to ferroptosis and found that all acute lung injury induced by ischemia-reperfusion, sepsis, radiation, drowning and oleic acid were involved in ferroptosis. We hope to provide a promising theoreticalbasis for the future diagnosis and treatment of acute lung injury by summarizing the mechanism of ferroptosis and its role in the pathogenesis of acute lung injury.

Key words: Ferroptosis, Acute lung injury, Oxidants, Reperfusion injury, Drowning, Review, Research progress

摘要：

铁死亡是一种以细胞内脂质过氧化物堆积为特征的新型细胞程序性死亡方式，其在多种疾病中发挥了重要作用。急性肺损伤是由多种原因引起的危重疾病，患者死亡率很高。随着对急性肺损伤机制研究的不断深入，更多证据表明铁死亡在急性肺损伤的发病机制中发挥了重要作用。本文通过归纳既往铁死亡相关研究成果，发现缺血再灌注、脓毒血症、放射线、淹溺、油酸诱发的急性肺损伤均有铁死亡的参与，并总结了铁死亡的作用机制及在急性肺损伤发病机制中的作用研究，以期能够给未来诊疗急性肺损伤提出有希望的治疗策略提供理论依据。

关键词: 铁死亡, 急性肺损伤, 过氧化物, 再灌注损伤, 溺水, 综述, 研究进展

ZHOU Sijiang,NING Zong. Research Progress of Ferroptosis in Acute Lung Injury[J]. Chinese General Practice, 2023, 26(03): 367-371. DOI: 10.12114/j.issn.1007-9572.2022.0186.
周思江,宁宗. 铁死亡在急性肺损伤中的研究进展[J]. 中国全科医学, 2023, 26(03): 367-371. DOI: 10.12114/j.issn.1007-9572.2022.0186.

Figures/Tables 3

References 45

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	调节机制	代表化合物
激动剂	抑制Xc-系统	Erastin及其衍生物^[11]，索拉非尼^[12]，HO-1^[9]，柳氮磺胺吡啶^[2]，谷氨酸酯^[2]，兰吡立松^[13]，麦芽糖铝^[14]等
	抑制/降解谷胱甘肽过氧化物酶4	RSL3及其衍生物^[15]，对乙酰氨基酚^[16]，六甲蜜胺^[17]，醉茄素A^[18]等
	其他	FINO₂^[19]，斯达汀^[20]，柠檬酸铁铵^[21]，青蒿琥酯^[22]，Cyst（e）inase^[23]，丁基硫^[2]等
拮抗剂	抑制铁积累	环吡酮胺^[24]，甲磺酸去铁胺^[25]，Dynasore^[26]，去铁胺^[27]，黄岑素^[28]等
	抑制酯质过氧化	齐留通，铁死亡抑制蛋白1^[29]，热休克蛋白β-1^[30]，Fer-1^[31]，Lip-1^[32]，维生素E^[8]，环己酰亚胺^[33]，氨基氧基乙酸^[34]，雷帕霉素^[35]等
	其他	七氟醚^[36]，西洋参酚^[9]等

	调节机制	代表化合物
激动剂	抑制Xc-系统	Erastin及其衍生物^[11]，索拉非尼^[12]，HO-1^[9]，柳氮磺胺吡啶^[2]，谷氨酸酯^[2]，兰吡立松^[13]，麦芽糖铝^[14]等
	抑制/降解谷胱甘肽过氧化物酶4	RSL3及其衍生物^[15]，对乙酰氨基酚^[16]，六甲蜜胺^[17]，醉茄素A^[18]等
	其他	FINO₂^[19]，斯达汀^[20]，柠檬酸铁铵^[21]，青蒿琥酯^[22]，Cyst（e）inase^[23]，丁基硫^[2]等
拮抗剂	抑制铁积累	环吡酮胺^[24]，甲磺酸去铁胺^[25]，Dynasore^[26]，去铁胺^[27]，黄岑素^[28]等
	抑制酯质过氧化	齐留通，铁死亡抑制蛋白1^[29]，热休克蛋白β-1^[30]，Fer-1^[31]，Lip-1^[32]，维生素E^[8]，环己酰亚胺^[33]，氨基氧基乙酸^[34]，雷帕霉素^[35]等
	其他	七氟醚^[36]，西洋参酚^[9]等

ALI模型	铁死亡抑制剂	作用靶点	信号通路
肺缺血再灌注损伤模型	iASPP、Lip-1	Nrf2、ACSL4	Nrf2/HIF-1α/TF
脓毒症相关肺损伤模型	Fer-1	Nrf2	Nrf2/HO-1/SLC7A11、Keap1/Nrf2/ARE
放射性肺损伤模型	Lip-1	GPX4	—
淹溺致ALI模型	Fer-1	Nrf2	—
油酸致ALI模型	—	PTGS2	—

ALI模型	铁死亡抑制剂	作用靶点	信号通路
肺缺血再灌注损伤模型	iASPP、Lip-1	Nrf2、ACSL4	Nrf2/HIF-1α/TF
脓毒症相关肺损伤模型	Fer-1	Nrf2	Nrf2/HO-1/SLC7A11、Keap1/Nrf2/ARE
放射性肺损伤模型	Lip-1	GPX4	—
淹溺致ALI模型	Fer-1	Nrf2	—
油酸致ALI模型	—	PTGS2	—