Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114201, Taiwan.
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City 114201, Taiwan.
Int J Mol Sci. 2024 Mar 5;25(5):3018. doi: 10.3390/ijms25053018.
Acute lung injury occurs in 20-25% of cases following traumatic brain injury (TBI). We investigated changes in lung transcriptome expression post-TBI using animal models and bioinformatics. Employing unilateral controlled cortical impact for TBI, we conducted microarray analysis after lung acquisition, followed by gene set enrichment analysis of differentially expressed genes. Our findings indicate significant upregulation of inflammation-related genes and downregulation of nervous system genes. There was enhanced infiltration of adaptive immune cells, evidenced by positive enrichment in Lung-Th1, CD4, and CD8 T cells. Analysis using the Tabula Sapiens database revealed enrichment in lung-adventitial cells, pericytes, myofibroblasts, and fibroblasts, indicating potential effects on lung vasculature and fibrosis. Gene set enrichment analysis linked TBI to lung diseases, notably idiopathic pulmonary hypertension. A Venn diagram overlap analysis identified a common set of 20 genes, with showing the most significant fold change. Additionally, we observed a significant increase in → production post-TBI using the L1000 library. Our study highlights the impact of brain trauma on lung injury, revealing crucial gene expression changes related to immune cell infiltration, cytokine production, and potential alterations in lung vasculature and fibrosis, along with a specific spectrum of disease influence.
颅脑损伤后，20-25%的患者会发生急性肺损伤。我们采用动物模型和生物信息学方法研究了颅脑损伤后肺转录组表达的变化。采用单侧皮质撞击法制作颅脑损伤模型，在获取肺组织后进行基因芯片分析，然后对差异表达基因进行基因集富集分析。研究结果表明，炎症相关基因显著上调，神经系统相关基因显著下调。适应性免疫细胞浸润增强，在 Lung-Th1、CD4 和 CD8 T 细胞中呈阳性富集。使用 Tabula Sapiens 数据库进行分析表明，肺外膜细胞、周细胞、肌成纤维细胞和成纤维细胞富集，提示可能对肺血管和纤维化有影响。基因集富集分析将颅脑损伤与肺部疾病联系起来，特别是特发性肺动脉高压。Venn 图重叠分析确定了 20 个共同基因，其中基因的 fold change 最显著。此外，我们还观察到 L1000 文库中颅脑损伤后 → 的产生显著增加。本研究强调了脑外伤对肺损伤的影响，揭示了与免疫细胞浸润、细胞因子产生以及肺血管和纤维化潜在改变相关的关键基因表达变化，并显示出特定的疾病影响谱。
