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生物信息学分析鉴定和验证脊髓损伤后的突触相关枢纽基因。

Identification and Validation of Synapse-related Hub Genes after Spinal Cord Injury by Bioinformatics Analysis.

机构信息

Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Department of Acupuncture and Moxibustion, Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

Comb Chem High Throughput Screen. 2024;27(4):599-610. doi: 10.2174/1386207326666230426151114.

Abstract

BACKGROUND

Spinal cord injury (SCI) is a neurological disease with high morbidity and mortality. Previous studies have shown that abnormally expressed synapse-related genes are closely related to the occurrence and development of SCI. However, little is known about the interaction of these aberrantly expressed genes and the molecular mechanisms that play a role in the injury response. Therefore, deeply exploring the correlation between synapse-related genes and functional recovery after spinal cord injury and the molecular regulation mechanism is of great significance.

METHODS

First, we selected the function GSE45006 dataset to construct three clinically meaningful gene modules by hierarchical clustering analysis in 4 normal samples and 20 SCI samples. Subsequently, we performed functional and pathway enrichment analyses of key modules.

RESULTS

The results showed that related module genes were significantly enriched in synaptic structures and functions, such as the regulation of synaptic membranes and membrane potential. A protein-protein interaction network (PPI) was constructed to identify 10 hub genes of SCI, and the results showed that Snap25, Cplx1, Stxbp1, Syt1, Rims1, Rab3a, Syn2, Syn1, Cask, Lin7b were most associated with SCI. Finally, these hub genes were further verified by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) in the spinal cord tissues of the blank group and SCI rats, and it was found that the expression of these hub genes was significantly decreased in the spinal cord injury compared with the blank group (P ≤ 0.05).

CONCLUSION

These results suggest that the structure and function of synapses play an important role after spinal cord injury. Our study helps to understand the underlying pathogenesis of SCI patients further and identify new targets for SCI treatment.

摘要

背景

脊髓损伤(SCI)是一种发病率和死亡率都很高的神经系统疾病。先前的研究表明,异常表达的突触相关基因与 SCI 的发生和发展密切相关。然而,人们对这些异常表达的基因之间的相互作用以及在损伤反应中发挥作用的分子机制知之甚少。因此,深入探讨突触相关基因与脊髓损伤后功能恢复之间的相关性以及分子调控机制具有重要意义。

方法

首先,我们选择功能 GSE45006 数据集,通过对 4 个正常样本和 20 个 SCI 样本进行层次聚类分析,构建了三个具有临床意义的基因模块。随后,我们对关键模块进行了功能和通路富集分析。

结果

结果表明,相关模块基因在突触结构和功能中显著富集,如突触膜和膜电位的调节。构建了一个蛋白质-蛋白质相互作用网络(PPI),以鉴定 10 个 SCI 的关键基因,结果表明 Snap25、Cplx1、Stxbp1、Syt1、Rims1、Rab3a、Syn2、Syn1、Cask 和 Lin7b 与 SCI 最相关。最后,通过空白组和 SCI 大鼠脊髓组织中的定量实时荧光聚合酶链反应(qRT-PCR)进一步验证了这些关键基因,发现与空白组相比,这些关键基因在脊髓损伤中的表达明显降低(P ≤ 0.05)。

结论

这些结果表明突触的结构和功能在脊髓损伤后发挥着重要作用。我们的研究有助于进一步了解 SCI 患者的潜在发病机制,并为 SCI 的治疗确定新的靶点。

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