Tang Yun-Liang, Fang Long-Jun, Zhong Ling-Yang, Jiang Jian, Dong Xiao-Yang, Feng Zhen
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
Neural Regen Res. 2020 Dec;15(12):2262-2269. doi: 10.4103/1673-5374.284996.
The exact mechanisms associated with secondary brain damage following traumatic brain injury (TBI) remain unclear; therefore, identifying the critical molecular mechanisms involved in TBI is essential. The 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. The 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 differentially expressed genes (DEGs) were identified in a Sprague-Dawley (SD) rat TBI model, 4 and 24 hours post-TBI, respectively. Functional enrichment analysis showed that the identified DEGs were significantly 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 inflammatory mediators. To validate the top five 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 performed. The 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. These identified pathways and key genes may provide insights into the molecular mechanisms of TBI and provide potential treatment targets for patients with TBI. This study was approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Nanchang University, China (approval No. 003) in January 2016.
创伤性脑损伤（TBI）后继发性脑损伤的具体机制仍不清楚；因此，确定TBI中涉及的关键分子机制至关重要。从基因表达综合数据库（GEO）下载了mRNA表达微阵列GSE2871。GSE2871总共包含31个大脑皮质样本，包括两个TBI后的时间点。该微阵列的特征为，在TBI后4小时有8个对照样本和7个TBI样本，在TBI后24小时有8个对照样本和8个TBI样本。在这项基于生物信息学的研究中，在Sprague-Dawley（SD）大鼠TBI模型中，分别在TBI后4小时和24小时鉴定出109个和66个差异表达基因（DEG）。功能富集分析表明，鉴定出的DEG在几个方面显著富集，如核因子-κB转录因子活性的正调控、丝裂原活化蛋白激酶信号通路、凋亡过程的负调控和肿瘤坏死因子信号通路。此外，具有高连接度的枢纽基因主要与炎症介质有关。为了验证排名前五的枢纽基因，采用重物坠落法建立了TBI大鼠模型，并对大脑皮质进行了实时定量聚合酶链反应分析。结果表明，与对照大鼠相比，Tnf-α、c-Myc、Spp1、Cxcl10、Ptprc、Egf、Mmp9和Lcn2在TBI大鼠中上调，而Fn1下调。在这些枢纽基因中，Fn1、c-Myc和Ptprc可能代表TBI的新型生物标志物或治疗靶点。这些鉴定出的通路和关键基因可能为TBI的分子机制提供见解，并为TBI患者提供潜在的治疗靶点。本研究于2016年1月获得中国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）。
