Luo Jiefeng, Chen Dingzhi, Mei Yujia, Li Hepeng, Qin Biyun, Lin Xiao, Chan Ting Fung, Lai Keng Po, Kong Deyan
Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, No 166 Dadaxuedong Road, Nanning, Guangxi, 530007, People's Republic of China.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
J Biol Eng. 2023 Aug 2;17(1):50. doi: 10.1186/s13036-023-00362-8.
Ischemic stroke accounts for 70-80% of all stroke cases, leading to over two million people dying every year. Poor diagnosis and late detection are the major causes of the high death and disability rate.
In the present study, we used the middle cerebral artery occlusion (MCAO) rat model and applied comparative transcriptomic analysis, followed by a systematic advanced bioinformatic analysis, including gene ontology enrichment analysis and Ingenuity Pathway Analysis (IPA). We aimed to identify novel biomarkers for the early detection of ischemic stroke. In addition, we aimed to delineate the molecular mechanisms underlying the development of ischemic stroke, in which we hoped to identify novel therapeutic targets for treating ischemic stroke.
In the comparative transcriptomic analysis, we identified 2657 differentially expressed genes (DEGs) in the brain tissue of the MCAO model. The gene enrichment analysis highlighted the importance of these DEGs in oxygen regulation, neural functions, and inflammatory and immune responses. We identified the elevation of angiopoietin-2 and leptin receptor as potential novel biomarkers for early detection of ischemic stroke. Furthermore, the result of IPA suggested targeting the inflammasome pathway, integrin-linked kinase signaling pathway, and Th1 signaling pathway for treating ischemic stroke.
The results of the present study provide novel insight into the biomarkers and therapeutic targets as potential treatments of ischemic stroke.
缺血性中风占所有中风病例的70 - 80%,每年导致超过200万人死亡。诊断不佳和检测延迟是高死亡率和高致残率的主要原因。
在本研究中,我们使用大脑中动脉闭塞(MCAO)大鼠模型并进行比较转录组分析,随后进行系统的高级生物信息学分析,包括基因本体富集分析和 Ingenuity 通路分析(IPA)。我们旨在识别用于早期检测缺血性中风的新型生物标志物。此外,我们旨在阐明缺血性中风发生发展的分子机制,希望从中识别出治疗缺血性中风的新型治疗靶点。
在比较转录组分析中,我们在MCAO模型的脑组织中鉴定出2657个差异表达基因(DEG)。基因富集分析突出了这些DEG在氧调节、神经功能以及炎症和免疫反应中的重要性。我们确定血管生成素 - 2和瘦素受体的升高是早期检测缺血性中风的潜在新型生物标志物。此外,IPA结果表明针对炎性小体通路、整合素连接激酶信号通路和Th1信号通路来治疗缺血性中风。
本研究结果为作为缺血性中风潜在治疗方法的生物标志物和治疗靶点提供了新的见解。