Li Tianzhi, Zhang Sijie, He Jinshan, Li Hongyan, Kang Jingsong
Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130021, China.
Antioxidants (Basel). 2025 May 30;14(6):665. doi: 10.3390/antiox14060665.
Ischemic stroke (IS) is the leading cause of disability and death worldwide, and its high incidence, disability and recurrence rates impose a heavy economic burden on families and society. Recent studies have shown that oxidative stress plays a key role in the pathophysiological mechanisms of ischemic stroke, not only participating in the onset and development of neuronal damage in the acute phase but also significantly influencing the long-term prognosis of ischemic stroke through molecular mechanisms, such as epigenetic modifications. However, the potential targets of oxidative stress-related genes in IS and their mechanisms of action remain to be elucidated. The aim of this study was to systematically analyse the function and significance of oxidative stress-related genes in IS. We obtained IS-related gene expression datasets from the GEO database and integrated known oxidative stress-related genes from the Genecards database for cross-analysis. Multidimensional feature screening using unsupervised consensus clustering and a series of machine learning algorithms led to the identification of the signature gene . The correlation between this gene and immune cell infiltration was assessed using MCPcounter and a potential therapeutic agent, glutathione, was identified. Binding was verified by molecular docking (MD) analysis. In addition, single-cell RNA sequencing data were analysed to further reveal expression in different cell types and its biological significance. Finally, we performed in vivo experiments using the Wistar rat middle cerebral artery occlusion (MCAO) model, and the results indicated that plays a key role in IS, providing a new theoretical basis and potential intervention target for the precise treatment of IS.
缺血性中风（IS）是全球致残和致死的主要原因，其高发病率、致残率和复发率给家庭和社会带来了沉重的经济负担。最近的研究表明，氧化应激在缺血性中风的病理生理机制中起关键作用，不仅参与急性期神经元损伤的发生和发展，还通过表观遗传修饰等分子机制显著影响缺血性中风的长期预后。然而，IS中氧化应激相关基因的潜在靶点及其作用机制仍有待阐明。本研究的目的是系统分析氧化应激相关基因在IS中的功能和意义。我们从GEO数据库中获取了与IS相关的基因表达数据集，并整合了来自Genecards数据库的已知氧化应激相关基因进行交叉分析。使用无监督一致性聚类和一系列机器学习算法进行多维度特征筛选，从而鉴定出标志性基因。使用MCPcounter评估该基因与免疫细胞浸润之间的相关性，并鉴定出一种潜在的治疗药物谷胱甘肽。通过分子对接（MD）分析验证结合情况。此外，对单细胞RNA测序数据进行分析，以进一步揭示其在不同细胞类型中的表达及其生物学意义。最后，我们使用Wistar大鼠大脑中动脉闭塞（MCAO）模型进行体内实验，结果表明 在IS中起关键作用，为IS的精准治疗提供了新的理论依据和潜在的干预靶点。
