GO analysis of upregulated DEPs.

ObjectiveRadiation-induced brain injury (RIBI) is a significant complication following radiotherapy for brain tumors, leading to neurocognitive deficits and other neurological impairments. This study aims to identify potential biomarkers and therapeutic targets for RIBI by utilizing advanced proteomic techniques to explore the molecular mechanisms underlying RIBI.MethodsA rat model of RIBI was established and subjected to whole-brain irradiation (30 Gy). Tandem mass tagging (TMT)-based quantitative proteomics, combined with high-resolution mass spectrometry, was used to identify differentially expressed proteins (DEPs) in the brain tissues of irradiated rats. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to identify the biological processes and pathways involved. Protein-protein interaction (PPI) networks were constructed to identify key hub proteins.ResultsA total of 35 DEPs were identified, including PHLDA3, APOE and CPE. GO enrichment analysis revealed that the DEPs were mainly involved in lipid transport, cell adhesion, and metabolic processes. KEGG analysis highlighted the enrichment of pathways related to metabolism, tight junctions, and PPAR signaling. APOE was identified as a key hub protein through PPI network analysis, indicating its potential role in RIBI pathophysiology. Immunohistochemistry further validated the increased expression of PHLDA3, APOE, and CPE in the brain tissue of irradiated rats.ConclusionThis study provides valuable insights into the molecular mechanisms of RIBI by identifying key proteins and their associated pathways. The findings suggest that these proteins, particularly APOE and PHLDA3, could serve as potential biomarkers and therapeutic targets for clinical intervention in RIBI. These results not only enhance our understanding of RIBI’s molecular pathology but also open new avenues for the development of targeted therapies to mitigate radiation-induced neurotoxicity.**研究目的**：放射诱导脑损伤（Radiation-induced brain injury, RIBI）是脑肿瘤放疗后常见的严重并发症，可引发神经认知功能缺损及其他神经功能障碍。本研究旨在借助先进的蛋白质组学技术，探究放射诱导脑损伤的分子机制，以筛选其潜在生物标志物与治疗靶点。 **研究方法**：本研究构建了放射诱导脑损伤大鼠模型，对其实施30 Gy全脑照射。采用基于串联质量标签（Tandem mass tagging, TMT）的定量蛋白质组学结合高分辨质谱技术，鉴定照射大鼠脑组织中的差异表达蛋白（differentially expressed proteins, DEPs）。通过基因本体（Gene Ontology, GO）富集分析与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路分析，明确差异表达蛋白参与的生物学过程与通路。构建蛋白质相互作用（protein-protein interaction, PPI）网络以筛选核心枢纽蛋白。 **研究结果**：共鉴定出35种差异表达蛋白，包括PHLDA3、APOE及CPE。GO富集分析显示，差异表达蛋白主要参与脂质转运、细胞黏附及代谢过程。KEGG通路分析结果显示，差异表达蛋白显著富集于代谢通路、紧密连接通路以及PPAR信号通路。通过PPI网络分析发现APOE为核心枢纽蛋白，提示其在放射诱导脑损伤的病理生理过程中发挥潜在作用。免疫组化实验进一步验证了照射大鼠脑组织中PHLDA3、APOE与CPE的表达水平显著升高。 **研究结论**：本研究通过鉴定关键蛋白及其相关通路，为放射诱导脑损伤的分子机制提供了重要见解。研究结果表明，上述蛋白尤其是APOE与PHLDA3可作为放射诱导脑损伤临床干预的潜在生物标志物与治疗靶点。本研究不仅加深了对放射诱导脑损伤分子病理的认识，同时为缓解放射诱导神经毒性的靶向治疗开发开辟了新方向。