Sevoflurane Postconditioning Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting SP1/ACSL4-Mediated Ferroptosis.

IF 2.7 4区医学 Q3 TOXICOLOGY

Human & Experimental Toxicology Pub Date : 2023-01-01 DOI:10.1177/09603271231160477

Ning Lyu, Xiaoyun Li

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引用次数: 3

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.

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七氟醚后处理通过抑制SP1/ acsl4介导的铁下垂减轻脑缺血再灌注损伤。

七氟醚是临床上最常用的麻醉剂，对脑缺血再灌注(I/R)损伤具有保护作用。本研究旨在阐明七氟醚后处理对脑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，模拟大脑I/R损伤。七氟醚后处理可减少I/R损伤后的神经功能缺损、脑梗死和铁下垂。有趣的是，七氟醚显著抑制OGD/R暴露的MACO大鼠和HT22细胞中特异性蛋白1 (SP1)的表达。SP1过表达减弱了七氟醚对OGD/ r处理的HT22细胞的神经保护作用，表现为细胞活力降低、细胞凋亡增加和caspase-3表达断裂。此外，染色质免疫沉淀和荧光素酶实验证实SP1直接结合到ACSL4启动子区域以增加其表达。此外，七氟醚通过SP1/ACSL4轴抑制铁下垂。总的来说，我们的研究描述了七氟醚通过下调SP1/ASCL4轴对脑I/R损伤的抗铁下沉作用。这些发现为脑I/R损伤的脑保护提供了新的视角，并为多种脑疾病提供了潜在的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human & Experimental Toxicology 医学-毒理学

CiteScore

5.70

自引率

3.60%

发文量

128

审稿时长

2.3 months

期刊介绍： Human and Experimental Toxicology (HET), an international peer reviewed journal, is dedicated to publishing preclinical and clinical original research papers and in-depth reviews that comprehensively cover studies of functional, biochemical and structural disorders in toxicology. The principal aim of the HET is to publish timely high impact hypothesis driven scholarly work with an international scope. The journal publishes on: Structural, functional, biochemical, and molecular effects of toxic agents; Studies that address mechanisms/modes of toxicity; Safety evaluation of novel chemical, biotechnologically-derived products, and nanomaterials for human health assessment including statistical and mechanism-based approaches; Novel methods or approaches to research on animal and human tissues (medical and veterinary patients) investigating functional, biochemical and structural disorder; in vitro techniques, particularly those supporting alternative methods