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高压氧治疗减轻脊髓损伤的机制:全基因组转录组分析

The mechanism by which hyperbaric oxygen treatment alleviates spinal cord injury: genome-wide transcriptome analysis.

作者信息

Sun Zhen-Cheng, Liang Fang, Yang Jing, Hai Yong, Su Qing-Jun, Liu Xue-Hua

机构信息

Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

出版信息

Neural Regen Res. 2022 Dec;17(12):2737-2742. doi: 10.4103/1673-5374.339498.

Abstract

Accumulating studies have demonstrated that hyperbaric oxygen (HBO) treatment alleviates spinal cord injury (SCI). However, the underlying mechanism by which HBO alleviates SCI remains to be elucidated. In this study, we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI. We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice. We found 76 differentially co-expressed genes in sham-operated mice, SCI mice, and HBO-treated SCI mice. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component, biological process, and molecular function. We also found enriched functional pathways including ferroptosis, calcium signaling pathway, serotonergic synapse, hypoxia-inducible factor-1 signaling pathway, cholinergic synapse, and neuroactive ligand-receptor interaction. We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1 (heat shock protein beta 1), Hmox1 (heme oxygenase 1), Ftl1 (ferritin light polypeptide 1), Tnc (tenascin C) and Igfbp3 (insulin-like growth factor binding protein 3) and increased the expression of Slc5a7 (solute carrier family 5 choline transporter member 7) after SCI. These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment. Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention.

摘要

越来越多的研究表明,高压氧(HBO)治疗可减轻脊髓损伤(SCI)。然而,HBO减轻SCI的潜在机制仍有待阐明。在本研究中,我们在脊髓损伤后1周通过高通量RNA测序对脊髓损伤小鼠和接受HBO治疗的小鼠的脊髓进行了全基因组转录谱分析。我们还比较了脊髓损伤小鼠和假手术小鼠的全基因组转录谱。我们在假手术小鼠、脊髓损伤小鼠和HBO治疗的脊髓损伤小鼠中发现了76个差异共表达基因。通过基因本体论和京都基因与基因组百科全书富集分析,我们从细胞成分、生物学过程和分子功能的角度确定了这些差异表达基因的生物学特征。我们还发现了富集的功能途径,包括铁死亡、钙信号通路、5-羟色胺能突触、缺氧诱导因子-1信号通路、胆碱能突触和神经活性配体-受体相互作用。我们进行了定量逆转录-聚合酶链反应,并验证了HBO治疗在脊髓损伤后降低了Hspb1(热休克蛋白β1)、Hmox1(血红素加氧酶1)、Ftl1(铁蛋白轻链多肽1)、Tnc(腱生蛋白C)和Igfbp3(胰岛素样生长因子结合蛋白3)的表达,并增加了Slc5a7(溶质载体家族5胆碱转运体成员7)的表达。这些结果揭示了HBO治疗后损伤脊髓的全基因组转录谱。我们的发现有助于更好地理解HBO治疗SCI的机制,并可能为SCI干预提供新的靶点。

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