据报道，电磁脉冲（EMP）辐射对海马神经元有害。然而,EMP诱导的神经元损伤的潜在机制尚不清楚.在本文中,第一次,我们试图研究铁凋亡在EMP诱导的神经元损伤中的作用及其潜在机制。用大鼠模型进行体内研究，以检查铁性凋亡和EMP诱导的海马神经元损伤的关系。此外，用HT22神经元进行体外研究，以研究EMP诱导的神经元铁性凋亡的潜在机制。体内实验结果表明,EMP可诱发大鼠学习记忆障碍,对线粒体的铁细胞形态损伤，丙二醛（MDA）和铁的积累，前列腺素-内过氧化物合酶2（PTGS2）mRNA的过表达，大鼠海马GPX4蛋白下调。体外实验结果表明EMP能诱导神经元死亡,MDA积累，铁过载，PTGS2过表达,和HT22神经元中的GPX4下调。这些不良反应可以通过脂质过氧化物清除剂铁抑制素-1或GPX4的过表达来逆转。这些结果表明，EMP辐射可以通过脂质过氧化物积累和GSH/GPX4轴下调的恶性循环诱导海马神经元的铁凋亡。脂质过氧化物和GSH/GPX4轴为EMP诱导的海马神经元损伤提供了潜在的有效干预靶点。
Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its underlying mechanism. In vivo studies were conducted with a rat model to examine the association of ferroptosis and EMP-induced hippocampal neuronal damage. Moreover, in vitro studies were conducted with HT22 neurons to investigate the underlying mechanism of EMP-induced neuronal ferroptosis. In vivo results showed that EMP could induce learning and memory impairment of rats, ferroptotic morphological damages to mitochondria, accumulation of malonaldehyde (MDA) and iron, overexpression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, and downregulation of GPX4 protein in rat hippocampus. In vitro results showed that EMP could induce neuronal death, MDA accumulation, iron overload, PTGS2 overexpression, and GPX4 downregulation in HT22 neurons. These adverse effects could be reversed by either lipid peroxides scavenger ferrostatin-1 or overexpression of GPX4. These results suggest that EMP radiation can induce ferroptosis in hippocampal neurons via a vicious cycle of lipid peroxides accumulation and GSH/GPX4 axis downregulation. Lipid peroxides and the GSH/GPX4 axis provide potential effective intervention targets to EMP-induced hippocampal neuronal damage.
