Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. Understanding the molecular mechanisms underlying ICH and its severe form is crucial for developing effective therapeutic strategies. This study investigates transcriptomic alterations in rodent models of ICH and severe intracerebral hemorrhage to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to intracerebral hemorrhage and severe intracerebral hemorrhage rats. We further employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the different molecular pathways involved. Using comprehensive RNA sequencing and bioinformatics analyses, we identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, intracerebral hemorrhage, and severe intracerebral hemorrhage groups in the upregulated genes group, and 1196 common genes in the downregulated genes. A volcano plot comparing the groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.脑出血（intracerebral hemorrhage, ICH）是一类伴随显著发病率与死亡率的危及生命的病症。阐明脑出血及其重症亚型的分子机制，对于开发高效治疗策略至关重要。本研究针对脑出血及重症脑出血的啮齿类动物模型开展转录组改变分析，以期揭示出血性脑损伤相关的遗传通路。本研究实施了主成分分析（principal component analysis），结果显示正常大鼠与脑出血、重症脑出血大鼠的主成分分布存在显著差异。本研究进一步采用热图（heatmap）与火山图（volcano plot）筛选差异表达基因，并通过柱状图（bar plot）与KEGG通路分析（Kyoto Encyclopedia of Genes and Genomes pathway analysis）阐明相关分子通路。通过全面的RNA测序（RNA sequencing）与生物信息学分析，本研究在脑出血及重症脑出血模型中均筛选到大量差异表达基因。研究结果显示，在上调基因集中，正常组、脑出血组与重症脑出血组共存在5679个共有基因；而下调基因集中则存在1196个共有基因。组间对比的火山图进一步凸显了多个共有基因，包括PDPN、TIMP1、SERPINE1、TUBB6以及CD44。上述研究结果凸显了炎症、氧化应激与神经元损伤相关基因之间的复杂相互作用。此外，通路富集分析揭示了与脑出血发病机制相关的关键信号通路，包括肿瘤坏死因子（TNF）信号通路、内质网蛋白质加工、丝裂原活化蛋白激酶（MAPK）信号通路以及Fcγ受体介导的吞噬作用。