Department of Neurosurgery, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Brain Behav. 2022 Aug;12(8):e2722. doi: 10.1002/brb3.2722. Epub 2022 Jul 27.
To investigate the role and mechanism of protein kinase R (PKR) in subarachnoid hemorrhage (SAH)-mediated ferroptosis.
A rat SAH model was constructed and treated with PKR inhibitor C16 to observe SAH and neurological impairment in rats and to detect malonaldehyde (MDA), iron ions content, ferritin heavy polypeptide 1 (FTH1) and glutathione peroxidase 4 (GPX4), and other related ferroptosis indicators in brain tissue. RNA sequencing analysis was used to investigate the mechanism of PKR, affecting the ferroptosis network of SAH.
SAH caused severe fundic hemorrhage, neurological impairment, MDA and iron ion accumulation, and significant decrease in GPX4 and FTH1 levels in rats. C16 treatment significantly improved the above signs caused by SAH. By RNA-seq analysis, brain tissue of SAH-treated rats with SAH and C16 differentially expressed mRNA target genes enriched in stress response and organic developmental signaling pathways.
Inhibition of PKR may improve cerebral injury after SAH by inhibiting ferroptosis, and RNA sequencing staged its mechanism of action may be related to the stress response.
探讨蛋白激酶 R（PKR）在蛛网膜下腔出血（SAH）介导的铁死亡中的作用和机制。
构建大鼠 SAH 模型，并给予 PKR 抑制剂 C16 处理，观察大鼠 SAH 和神经损伤情况，并检测脑组织中丙二醛（MDA）、铁离子含量、铁蛋白重链 1（FTH1）和谷胱甘肽过氧化物酶 4（GPX4）等相关铁死亡指标。采用 RNA 测序分析探讨 PKR 影响 SAH 铁死亡网络的作用机制。
SAH 导致大鼠胃底出血严重，神经损伤，MDA 和铁离子蓄积，GPX4 和 FTH1 水平显著降低。C16 处理可明显改善 SAH 引起的上述征象。通过 RNA-seq 分析，SAH 处理大鼠脑组织中差异表达的 mRNA 靶基因富集在应激反应和有机发育信号通路中。
抑制 PKR 可能通过抑制铁死亡改善 SAH 后的脑损伤，RNA 测序分期其作用机制可能与应激反应有关。
