中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 155-161.doi: 10.4103/1673-5374.343886

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

串联质量标签标记定量蛋白质组学揭示炎症反应在小鼠创伤性脑损伤后发挥重要作用

  

  • 出版日期:2023-01-15 发布日期:2022-06-17
  • 基金资助:
    国家自然科学基金项目(81771327),神经系统损伤基础研究与临床转化平台(PXM2020_026280_000002)

Tandem Mass Tag-based proteomics analysis reveals the vital role of inflammation in traumatic brain injury in a mouse model

Jin-Qian Dong1, Qian-Qian Ge1, Sheng-Hua Lu1, Meng-Shi Yang1, Yuan Zhuang1, Bin Zhang1, Fei Niu2, Xiao-Jian Xu2, *, Bai-Yun Liu1, 2, 3, 4, *   

  1. 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 2Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; 3Center for Nerve Injury and Repair, Beijing Institute of Brain Disorders, Beijing, China; 4China National Clinical Research Center for Neurological Diseases, Beijing, China
  • Online:2023-01-15 Published:2022-06-17
  • Contact: Xiao-Jian Xu, PhD, xjianxu@163.com; Bai-Yun Liu, MD, PhD, liubaiyun1212@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81771327, and a grant for the Platform Construction of Basic Research and Clinical Translation of Nervous System Injury, China, No. PXM2020_026280_000002 (both to BYL).

摘要:

蛋白质组学是一种阐明疾病潜在机制和识别新生物标志物的强大工具,因此其可能帮助了解创伤性脑损伤的详细病理机制。因此实验对控制性皮质打击建立的急性期创伤性脑损伤小鼠模型在进行串联质量标签的定量蛋白质组学分析,已了解损伤皮质中蛋白质层面的变化。结果发现,在损伤后7d,与正常小鼠相比,创伤性脑损伤小鼠中有302种差异表达的蛋白。进一步GO和KEGG功能富集分析表明,这些差异表达蛋白主要参与炎症反应,包括补体和凝血级联以及趋化因子信号通路。而后的转录因子分析发现炎症相关转录因子NF-κB1、RelA、IRF1、STAT1和Spi1等可在创伤性脑损伤后继发性损伤中起关键作用,这进一步证实了其功能富集分析的结果。综上表明炎症相关蛋白和炎症反应是创伤性脑损伤的很有前景的干预靶点。

https://orcid.org/0000-0001-8204-2623 (Bai-Yun Liu)

关键词: 创伤性脑损伤, 亚急性期, 继发性损伤, 蛋白质组学, 串联质量标签, 质谱分析, 生物信息学, 神经炎症, 补体, 转录因子

Abstract: Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers. Therefore, it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury (TBI). In this study, we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of TBI. Our results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after injury. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses, including complement and coagulation cascades, as well as chemokine signaling pathways. Subsequent transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1, RelA, IRF1, STAT1, and Spi1 play pivotal roles in the secondary injury that occurs after TBI, which further corroborates the functional enrichment for inflammatory factors. Our results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI. 

Key words: bioinformatics, complement cascade, mass spectrometry, neuroinflammation, proteomics, secondary injury, subacute phase, tandem mass tag, transcription factor, traumatic brain injury