新生儿缺氧缺血性脑病中的铁死亡:从机制探索到治疗新思路  

Ferroptosis in Neonatal Hypoxic-Ischemic Encephalopathy:From Mechanism Exploration to New Therapeutic Approaches

作　　者：罗丽艳 张红 蒋巧稚 黑少鹤 李敏 Luo Liyan;Zhang Hong;Jiang Qiaozhi;Hei Shaohe;Li Min(Maternity and Child Healthcare Hospital of Dali Bai Autonomous Prefecture,Dali,Yunnan 671000)

机构地区：[1]大理白族自治州妇幼保健院,云南大理671000

出　　处：《科技与健康》2025年第4期69-72,共4页Technology and Health

基　　金：大理州科技计划项目基础研究专项“新生儿缺氧缺血性脑损伤中LPCAT3基因转录调控机制的研究”(20232901A020010)。

摘　　要：新生儿缺氧缺血性脑病(hypoxic-ischaemic encephalopathy,HIE)是围产期病情较为严重的脑损伤疾病,通常由分娩过程中的缺氧或血流受限引起,会影响新生儿的神经发育。HIE的病理机制复杂,包括氧化应激、神经炎症和程序性细胞死亡等。近年来,铁死亡(ferroptosis)作为一种新型的程序性细胞死亡方式,在HIE的病理中备受关注。铁死亡的核心特征是铁依赖的脂质过氧化,导致细胞内谷胱甘肽耗竭、谷胱甘肽过氧化物酶4(GPX4)失活和脂质过氧化物累积,引发神经元和胶质细胞的不可逆损伤,进一步加重HIE的脑损害。系统分析了铁死亡在HIE中的作用机制,重点分析了其与氧化应激和神经炎症的相互关系及其对脑细胞的影响,总结了铁死亡的分子机制及关键调控分子,并评估了其作为HIE治疗靶点的潜力。动物模型研究显示,通过抑制铁死亡相关分子,可以显著改善HIE引起的脑损伤。这些研究为HIE的治疗提供了新思路,未来有望通过精准靶向铁死亡关键分子的药物研发,为临床干预HIE提供更有效的治疗方法。Neonatal hypoxic-ischaemic encephalopathy(HIE)is a severe perinatal brain injury disease,usually caused by hypoxia or restricted bloodflow during childbirth,which can affect the neural development of neonates.The pathological mechanisms of HIE are complex,including oxidative stress,neuroinflammation,and programmed cell death.In recent years,ferroptosis,as a novel type of programmed cell death,has received much attention in the pathology of HIE.The core feature of ferroptosis is iron-dependent lipid peroxidation,leading to the depletion of intracellular glutathione,inactivation of glutathione peroxidase 4(GPX4),and accumulation of lipid peroxides,causing irreversible damage to neurons and glial cells and further aggravating the brain damage in HIE.This study systematically analyzes the mechanism of action of ferroptosis in HIE,focusing on its interrelationships with oxidative stress and neuroinflammation and its effects on brain cells.It also summarizes the molecular mechanisms of ferroptosis and key regulatory molecules and evaluates its potential as a therapeutic target for HIE.Studies on animal models have shown that by inhibiting ferroptosis-related molecules,the brain damage caused by HIE can be significantly improved.These studies provide new ideas for the treatment of HIE.In the future,it is expected that through the research and development of drugs that precisely target key molecules of ferroptosis,more effective treatment methods for clinical intervention in HIE can be provided.

关 键 词：铁死亡 新生儿缺氧缺血性脑病 脑损伤 氧化应激 

分 类 号：R72[医药卫生—儿科]