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通过微阵列分析鉴定脊髓损伤后分子通路的变化。

Identification of molecular pathway changes after spinal cord injury by microarray analysis.

作者信息

Zhang Haocong, Wang Yan

机构信息

Department of Orthopaedics, The General Hospital of PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.

出版信息

J Orthop Surg Res. 2016 Sep 15;11(1):101. doi: 10.1186/s13018-016-0437-3.

Abstract

BACKGROUND

Spinal cord injury (SCI) is highly related to the devastating sensory and motor dysfunction.

METHODS

The GSE45006 gene expression profile dataset was downloaded from Gene Expression Omnibus, which was collected from 24 rats including 20 animals with injured T7 spinal cords using an aneurysm clip impact-compression injury model and killed after 1 day, 3 days, 1 week, 2 weeks, and 8 weeks and four sham-operated rats. Differentially expressed genes (DEGs) between the injured rats at each time point and the sham-operated rats were screened. DEGs commonly detected throughout different time points were further identified, followed by comparing the expression level of these DEGs at each time point between the injured spinal cord samples and controls. Pathway enrichment analysis of the common DEGs was performed.

RESULTS

The difference in the expression level of 416 common DEGs was significant between the injured spinal cord samples and the controls at each time point (P < 0.05), with the most significant difference 1 day after SCI. The common DEGs were enriched in three pathways, namely Fcγ R-mediated phagocytosis, mitogen-activated protein kinase (MAPK) signaling pathway, and chemokine signaling pathway. AKT3 and RAC2 were enriched in all the three pathways; RAP1B in both MAPK signaling pathway and chemokine signaling pathway; and VAV1, LYN, and HCK in both Fcγ R-mediated phagocytosis and chemokine signaling pathway.

CONCLUSIONS

This study has confirmed the occurrence of neuronal death, inflammation, and neuronal regeneration after SCI. AKT3, RAC2, VAV1, RAP18, LYN, and HCK may have critical roles in the pathological responses to SCI.

摘要

背景

脊髓损伤(SCI)与严重的感觉和运动功能障碍高度相关。

方法

从基因表达综合数据库下载GSE45006基因表达谱数据集,该数据集收集自24只大鼠,其中包括20只使用动脉瘤夹撞击压缩损伤模型造成T7脊髓损伤的动物,并在1天、3天、1周、2周和8周后处死,另外还有4只假手术大鼠。筛选每个时间点损伤大鼠与假手术大鼠之间的差异表达基因(DEG)。进一步鉴定在不同时间点均能检测到的DEG,然后比较这些DEG在损伤脊髓样本与对照之间每个时间点的表达水平。对常见DEG进行通路富集分析。

结果

每个时间点损伤脊髓样本与对照之间416个常见DEG的表达水平差异均具有统计学意义(P < 0.05),脊髓损伤后1天差异最为显著。常见DEG富集于三条通路,即Fcγ R介导的吞噬作用、丝裂原活化蛋白激酶(MAPK)信号通路和趋化因子信号通路。AKT3和RAC2在所有三条通路中均有富集;RAP1B在MAPK信号通路和趋化因子信号通路中均有富集;VAV1、LYN和HCK在Fcγ R介导的吞噬作用和趋化因子信号通路中均有富集。

结论

本研究证实了脊髓损伤后神经元死亡、炎症和神经元再生的发生。AKT3、RAC2、VAV1、RAP18、LYN和HCK可能在脊髓损伤的病理反应中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115f/5024485/2c9323a54e9b/13018_2016_437_Fig1_HTML.jpg

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