Ren Bin, Liang Jifang, Yang Leifang, Wei Xiaocong, Guo Min, Li Hong
Department of Neurosurgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China.
Department of Intensive Care Unit, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China.
Front Aging Neurosci. 2025 Apr 25;17:1531317. doi: 10.3389/fnagi.2025.1531317. eCollection 2025.
Oxidative stress is a pivotal mechanism implicated in the onset of traumatic brain injury (TBI), yet its precise role remains elusive. This study aims to elucidate the potential molecular interactions between key genes associated with oxidative stress and their influence on TBI pathogenesis.
TBI dataset and oxidative stress-related genes sourced from Public databases. Differential expression analysis and machine learning models were executed to select key genes, which were further validated using receiver operating characteristic (ROC) curves. A nomogram was constructed for diagnostic prediction, and enrichment analysis explored pathways associated with key genes. Immune infiltration analysis and regulatory network construction were conducted. Molecular validation included RT-qPCR and Western blotting using rat brain tissue to assess gene and protein expression levels.
In our study, we identified 400 differentially expressed genes (DEGs) between TBI and normal samples, including 20 oxidative stress-related genes. Machine learning analysis highlighted AKR1C2, QDPR, CYP3A5, CNTF, and PNPT1 as key genes with diagnostic potential (AUC > 0.6). Functional analysis revealed significant involvement of these genes in immune processes and metabolic regulation. Further, immune cell infiltration analysis showed notable differences in effector memory CD8 T cells. Molecular validation through RT-qPCR and Western blot confirmed the overexpression of key genes PNPT1 and QDPR in TBI models, substantiating their potential role in TBI pathology.
Our study revealed the potential mechanisms of action for PNPT1 and QDPR in TBI, offering valuable insights into their roles in TBI pathology. These findings opened new avenues for future therapeutic strategies in TBI treatment.
氧化应激是创伤性脑损伤（TBI）发病机制中的一个关键机制，但其确切作用仍不清楚。本研究旨在阐明与氧化应激相关的关键基因之间潜在的分子相互作用及其对TBI发病机制的影响。
从公共数据库获取TBI数据集和氧化应激相关基因。进行差异表达分析和机器学习模型以选择关键基因，并使用受试者工作特征（ROC）曲线进一步验证。构建列线图用于诊断预测，并进行富集分析以探索与关键基因相关的通路。进行免疫浸润分析和调控网络构建。分子验证包括使用大鼠脑组织进行RT-qPCR和蛋白质印迹，以评估基因和蛋白质表达水平。
在我们的研究中，我们鉴定出TBI与正常样本之间有400个差异表达基因（DEG），其中包括20个氧化应激相关基因。机器学习分析突出显示AKR1C2、QDPR、CYP3A5、CNTF和PNPT1为具有诊断潜力的关键基因（AUC>0.6）。功能分析表明这些基因在免疫过程和代谢调节中显著参与。此外，免疫细胞浸润分析显示效应记忆CD8 T细胞存在显著差异。通过RT-qPCR和蛋白质印迹进行的分子验证证实了关键基因PNPT1和QDPR在TBI模型中的过表达，证实了它们在TBI病理中的潜在作用。
我们的研究揭示了PNPT1和QDPR在TBI中的潜在作用机制，为它们在TBI病理中的作用提供了有价值的见解。这些发现为TBI治疗的未来治疗策略开辟了新途径。
