中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (12): 2737-2742.doi: 10.4103/1673-5374.339498

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

高压氧治疗缓解脊髓损伤的潜在机制:全基因组转录组分析

  

  • 出版日期:2022-12-15 发布日期:2022-05-05
  • 基金资助:
    北京自然科学基金(7202055)

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

Zhen-Cheng Sun1, Fang Liang2, Jing Yang2, Yong Hai1, Qing-Jun Su1, *, Xue-Hua Liu2, *   

  1. 1Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; 2Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
  • Online:2022-12-15 Published:2022-05-05
  • Contact: Qing-Jun Su, MD, qjsurex@sohu.com; Xue-Hua Liu, MD, liuxuehua_1981@163.com.
  • Supported by:
    This study was supported by the Natural Science Foundation of Beijing, No. 7202055 (to XHL). 

摘要:

越来越多的研究表明,高压氧(HBO)可用于治疗脊髓损伤;然而,其潜在作用机制仍有待进一步阐明。实验首先通过高通量RNA测序对经/未经高压氧治疗脊髓挫伤小鼠伤后第1周的脊髓组织进行了全基因组分析,并与假手术组进行对照,结果发现3组有76个差异共表达基因。紧接着通过对这些差异表达基因进行GO和KEGG通路富集分析,从细胞成分、分子功能、生物过程3个层面阐明了这些差异基因的生物学特性,并且发现了显著富集的功能通路,如:铁死亡、钙信号通路、5-羟色胺能突触、缺氧诱导因子信号通路、胆碱能突触和神经活性配体-受体相互作用。最后通过实时定量PCR进行验证,证明高压氧治疗可能通过抑制休克蛋白β1(Hspb1)、血红素加氧酶1(Hmox1)、铁蛋白轻多肽1(Ftl1)、肌腱蛋白C(Tnc)、胰岛素样生长因子结合蛋白3(Igfbp3)的表达的表达及促进溶质载体家族5胆碱转运器成员7(SLC5a7)基因的表达减轻了脊髓损伤后的继发性损伤,促进了损伤小鼠肢体功能的恢复。实验揭示了高压氧治疗后损伤脊髓的全基因表达谱,这些结果有助于更好地理解高压氧治疗脊髓损伤的机制,并为脊髓损伤的干预提供了潜在靶点。

https://orcid.org/0000-0001-9563-138X (Qing-Jun Su); https://orcid.org/0000-0002-1385-4852 (Xue-Hua Liu)

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.

Key words: Ftl1, genome-wide transcriptome, Hmox1, Hspb1, hyperbaric oxygen, Igfbp3, Slc5a7, spinal cord injury, Tnc