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南京医科大学学报(自然科学版) 第42卷第02期
·270 · Journal of Nanjing Medical University(Natural Sciences) 2022年02月
·综 述·
铁死亡在颅脑外伤中的研究进展
包钟元 ,季 晶 1*
1,2
南京医科大学第一附属医院神经外科,江苏 南京 210029;南京医科大学附属无锡市第二人民医院神经外科,江苏 无
1 2
锡 214000
[摘 要] 颅脑外伤(traumatic brain injury,TBI)是由外力引起的大脑结构和生理功能破坏的损伤性疾病。它是全世界导致
患者死亡和残疾的主要原因。颅脑外伤包括原发性和继发性损伤。铁含量的过度积累和铁死亡进程高度参与继发性脑损伤
的病理生理过程。铁死亡是一种可调节的程序性细胞死亡,因为脑内铁积累增加导致脂质过氧化、活性氧(reactive oxygen spe⁃
cies,ROS)产生、线粒体功能障碍和神经炎症反应,从而导致神经元的损伤。因此,减少铁的过度积累和抑制脂质过氧化等因
素可能是一种有前途的治疗方法。铁螯合剂可以消除过量的铁,减轻部分颅脑外伤的临床症状。文章将重点讨论在颅脑外伤
中的铁含量和铁死亡的机制,以拓宽对铁螯合剂治疗脑外伤的认识,为进一步的颅脑外伤治疗寻找新的研究方向。
[关键词] 颅脑外伤;铁死亡;脂质过氧化;分子靶向治疗
[中图分类号] R651.1 [文献标志码] A [文章编号] 1007⁃4368(2022)02⁃270⁃09
doi:10.7655/NYDXBNS20220221
The role of ferroptosis in traumatic brain injury
1,2 1*
BAO Zhongyuan ,JI Jing
1 Department of Neurosurgery,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029;
2 Department of Neurosurgery,Wuxi No.2 People’s Hospital Affiliated to Nanjing Medical University,Wuxi 214000,
China
[Abstract] Traumatic brain injury(TBI)is a structural and physiological disruption of brain function caused by external forces. It is
the leading cause of death and disability worldwide. TBI includes both primary and secondary injuries. Excessive iron accumulation
and ferroptosis are highly involved in the pathophysiological process of secondary brain injury. Ferroptosis is a form of regulatory cell
death,characteristic as increased iron accumulation,lipid peroxidation,reactive oxygen species(ROS)production,mitochondrial
dysfunction and neuroinflammatory responses,resulting in cellular and neuronal damage. For this reason,eliminating factors like
excessive accumulation of iron and inhibiting lipid peroxidation may be a promising therapy approach. Iron chelators can be used to
eliminate excess iron and to alleviate some of the clinical manifestations of TBI. In this review,it was focused on the mechanisms of
iron and ferroptosis involved in the manifestations of TBI,broadening our understanding of the use of iron chelators for TBI,better
seeking new research directions for further treatment of TBI.
[Key word] traumatic brain injury;ferroptosis;lipid peroxidation;molecular targeted therapy
[J Nanjing Med Univ,2022,42(02):270⁃278]
颅脑外伤(traumatic brain injury,TBI)是全球成 除了外伤造成的直接损伤外,患者在创伤后通常会
年人死亡和残疾的重要原因之一。仅在中国,以人口 出现严重和广泛的神经元坏死、脑组织水肿、血脑
为基础的TBI死亡率约达到每10万人中有13例 。 屏障(blood brain barrier,BBB)破坏、氧化应激加剧
[1]
和过度活跃的炎症反应。这些不利因素的恶性循
[2]
[基金项目] 国家自然科学基金(81972153) 环最终导致死亡、残疾和植物人状态 。有创伤性
∗ 颅脑损伤背景的老年人更有可能发生认知障碍、痴
通信作者(Corresponding author),E⁃mail:jijing@njmu.edu.cn