Abstract：
Sevoflurane is the most commonly used anesthetic in clinical practice and exerts a protective effect on cerebral ischemia-reperfusion (I/R) injury. This study aims to elucidate the molecular mechanism by which sevoflurane postconditioning protects against cerebral I/R injury. Oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro and the middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. Sevoflurane postconditioning reduced neurological deficits, cerebral infarction, and ferroptosis after I/R injury. Interestingly, sevoflurane significantly inhibited specificity protein 1 (SP1) expression in MACO rats and HT22 cells exposed to OGD/R. SP1 overexpression attenuated the neuroprotective effects of sevoflurane on OGD/R-treated HT22 cells, evidenced by reduced cell viability, increased apoptosis, and cleaved caspase-3 expression. Furthermore, chromatin immunoprecipitation and luciferase experiments verified that SP1 bound directly to the ACSL4 promoter region to increase its expression. In addition, sevoflurane inhibited ferroptosis via SP1/ACSL4 axis. Generally, our study describes an anti-ferroptosis effect of sevoflurane against cerebral I/R injury via downregulating the SP1/ASCL4 axis. These findings suggest a novel sight for cerebral protection against cerebral I/R injury and indicate a potential therapeutic approach for a variety of cerebral diseases.
摘要：
七氟醚是临床上最常用的麻醉药,对脑缺血再灌注损伤具有保护作用。本研究旨在阐明七氟醚后处理保护脑I/R损伤的分子机制。建立体外氧糖剥夺/再灌注（OGD/R）模型和体内大脑中动脉闭塞（MCAO）模型，以模拟脑I/R损伤。七氟醚后处理减少神经功能缺损，脑梗塞,I/R损伤后的铁性凋亡。有趣的是,七氟醚显著抑制暴露于OGD/R的MACO大鼠和HT22细胞中特异性蛋白1(SP1)的表达。SP1过表达减弱七氟醚对OGD/R处理的HT22细胞的神经保护作用,由细胞活力降低证明，细胞凋亡增加，和裂解的caspase-3表达。此外，染色质免疫沉淀和荧光素酶实验证实SP1直接结合ACSL4启动子区以增加其表达。此外,七氟醚通过SP1/ACSL4轴抑制铁凋亡。一般来说,我们的研究描述了七氟醚通过下调SP1/ASCL4轴对抗脑I/R损伤的抗铁凋亡作用.这些发现表明了针对脑I/R损伤的脑保护的新观点，并为各种脑疾病提供了潜在的治疗方法。
