Liu Tongye, Li Xinhe, Cui Yiteng, Meng Pingping, Zeng Guanghui, Wang Yuyang, Wang Qiang
Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Sports Medicine, Qingdao University Medical College, Qingdao, China.
Front Neurosci. 2021 Jun 7;15:661663. doi: 10.3389/fnins.2021.661663. eCollection 2021.
Intracerebral hemorrhage (ICH) is a dangerous neurological disease. The mechanism of ferroptosis in ICH remains unclear. Using bioinformatics analysis, we aimed to identify the key molecules involved in ferroptosis and provide treatment targets for ICH to further explore the mechanism of ferroptosis in ICH. GSE24265 was downloaded from the Gene Expression Omnibus (GEO) dataset and intersected with ferroptosis genes. A total of 45 differentially expressed genes (DEGs) were selected, most of which were involved in the TNF signaling pathway and oxidative stress response. Key modules constructed by the protein-protein interaction (PPI) network analysis and screening of genes related to the TNF signaling pathway led to the confirmation of the following genes of interest: , , , , and . Moreover, was one of the key genes related to TNF signaling and oxidative stress, and it may play an important role in ferroptosis after cerebral hemorrhage. The -related molecules included , , , , , , , , , , , and We also generated a hemorrhage rat model, which was used to conduct exercise intervention in ICH rats, and qRT-PCR was used to assess the expression levels of our genes of interest. The mRNA levels after cerebral hemorrhage showed that , , , and were upregulated, whereas was downregulated. Treadmill training increased the expression of anti-inflammatory molecules and and reduced the expression of , and , indicating that treadmill training may be utilized as antioxidant therapy to decrease neuronal ferroptosis. The results of this study indicated that the -related mRNA-miRNA-lncRNA interaction chain could be potentially employed as a biomarker of the inception and progression of ferroptosis after cerebral hemorrhage.
脑出血(ICH)是一种危险的神经系统疾病。脑出血中铁死亡的机制尚不清楚。通过生物信息学分析,我们旨在识别参与铁死亡的关键分子,并为脑出血提供治疗靶点,以进一步探索脑出血中铁死亡的机制。从基因表达综合数据库(GEO)下载GSE24265数据集,并与铁死亡基因进行交集分析。共筛选出45个差异表达基因(DEGs),其中大部分参与肿瘤坏死因子(TNF)信号通路和氧化应激反应。通过蛋白质-蛋白质相互作用(PPI)网络分析构建关键模块,并筛选与TNF信号通路相关的基因,从而确定了以下感兴趣的基因: 、 、 、 、 。此外, 是与TNF信号和氧化应激相关的关键基因之一,它可能在脑出血后的铁死亡中发挥重要作用。与 相关的分子包括 、 、 、 、 、 、 、 、 、 、 。我们还建立了脑出血大鼠模型,用于对脑出血大鼠进行运动干预,并采用实时定量聚合酶链反应(qRT-PCR)评估我们感兴趣基因的表达水平。脑出血后的mRNA水平显示, 、 、 、 上调,而 下调。跑步机训练增加了抗炎分子 和 的表达,降低了 、 和 的表达,表明跑步机训练可作为抗氧化疗法来减少神经元铁死亡。本研究结果表明, 相关的mRNA-微小RNA(miRNA)-长链非编码RNA(lncRNA)相互作用链可能作为脑出血后铁死亡发生和进展的生物标志物。