中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (12): 2262-2269.doi: 10.4103/1673-5374.284996

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

创伤性脑损伤的关键基因及通路：生物信息学分析与动物实验鉴定

  

  • 出版日期:2020-12-15 发布日期:2020-08-05
  • 基金资助:

    国家自然科学基金项目（81860409，81660382），江西省研究生创新基金项目（YC2019-B036）

Hub genes and key pathways of traumatic brain injury: bioinformatics analysis and in vivo validation

Yun-Liang Tang, Long-Jun Fang, Ling-Yang Zhong, Jian Jiang, Xiao-Yang Dong, Zhen Feng    

  1. Department of Rehabilitation Medicine, Te First Afliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
  • Online:2020-12-15 Published:2020-08-05
  • Contact: Zhen Feng, PhD, fengzhen@email.ncu.edu.cn.
  • Supported by:
    Tis study was supported by the National Natural Science Foundation of China, Nos. 81860409 (to ZF), 81660382 (to ZF), and Graduate Students Innovation Fund Project in Jiangxi Province of China, No. YC2019-B036 (to YLT).

PDF

260

摘要：

创伤性脑损伤后的继发性脑损伤，其机制尚不清楚，实验设计旨在进一步明确创伤性脑损伤的关键分子机制。（1）首先收集GEO数据集中的mRNA表达微阵列（GSE2871）数据，这些数据包含31个SD大鼠大脑皮质样本，其中TBI后4h时有8个对照样本和7个TBI样本；24h时有8个对照样本和8个TBI样本；（2）以生物信息学分析发现，在TBI后4h和24h各筛选了109个和66个差异表达基因。功能富集分析结果表明，差异表达基因主要参与NF-κB转录因子活性和MAPK信号通路正调控、凋亡过程和肿瘤坏死因子信号通路的负调控等，而关键基因主要与炎症递质有关；（3）为了验证前5位关键基因的准确性，继而以重物打击法建立创伤性脑损伤大鼠模型，对大脑皮质行实时定量PCR分析，结果显示，与对照大鼠相比，创伤性脑损伤大鼠Tnf-α、c-Myc、Spp1、Cxcl10、Ptprc、Egf、Mmp9和Lcn2基因表达上调，Fn1基因表达下调。在这些关键基因中，Fn1、c-Myc和Ptprc基因可能是创伤性脑损伤新的生物标志物或治疗靶点；（4）这些已被识别的信号途径和关键基因可能为创伤性脑损伤分子机制探究提供帮助，并为创伤性脑损伤患者提供潜在的治疗靶点。实验于2016年1月经南昌大学第一附属医院实验动物伦理委员会批准（批准号003）。

orcid: 0000-0003-2201-7797 (Zhen Feng)

关键词: 生物信息学, 差异表达基因, DEG, 关键基因, 分子机制, 创伤性脑损伤, 炎症, KEGG通路

Abstract: Te exact mechanisms associated with secondary brain damage following traumatic brain injury (TBI) remain unclear; therefore, identify- ing the critical molecular mechanisms involved in TBI is essential. Te mRNA expression microarray GSE2871 was downloaded from the Gene Expression Omnibus (GEO) repository. GSE2871 comprises a total of 31 cerebral cortex samples, including two post-TBI time points. Te microarray features eight control and seven TBI samples, from 4 hours post-TBI, and eight control and eight TBI samples from 24 hours post-TBI. In this bioinformatics-based study, 109 and 66 diferentially expressed genes (DEGs) were identifed in a Sprague-Dawley (SD) rat TBI model, 4 and 24 hours post-TBI, respectively. Functional enrichment analysis showed that the identifed DEGs were signif- cantly enriched in several terms, such as positive regulation of nuclear factor-κB transcription factor activity, mitogen-activated protein kinase signaling pathway, negative regulation of apoptotic process, and tumor necrosis factor signaling pathway. Moreover, the hub genes with high connectivity degrees were primarily related to infammatory mediators. To validate the top fve hub genes, a rat model of TBI was established using the weight-drop method, and real-time quantitative polymerase chain reaction analysis of the cerebral cortex was per- formed. Te results showed that compared with control rats, Tnf-α, c-Myc, Spp1, Cxcl10, Ptprc, Egf, Mmp9, and Lcn2 were upregulated, and Fn1 was downregulated in TBI rats. Among these hub genes, Fn1, c-Myc, and Ptprc may represent novel biomarkers or therapeutic targets for TBI. Tese identifed pathways and key genes may provide insights into the molecular mechanisms of TBI and provide potential treat- ment targets for patients with TBI. Tis study was approved by the Experimental Animal Ethics Committee of the First Afliated Hospital of Nanchang University, China (approval No. 003) in January 2016.

Key words: bioinformatics, DEGs, diferentially expressed genes, Gene Ontology, hub genes, infammation, Kyoto Encyclopedia of Genes and Genomes, molecular mechanism, traumatic brain injury