Beijing Key Laboratory for Radiobiology, Department of Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Beijing Key Laboratory for Radiobiology, Department of Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, China; Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China.
Toxicol Lett. 2024 Aug;399:43-51. doi: 10.1016/j.toxlet.2024.07.911. Epub 2024 Jul 18.
In the event of a nuclear or radiation accident, rapid identification is required for those who exposed to potentially lethal dose irradiation. However, existing techniques are not adequate for the classification of lethal injury. Several studies have explored the potential of miRNAs as biomarkers for ionizing radiation injury, however, there are few miRNAs with specific expression for lethal radiation injury. Therefore, the aim of this study was to screen and validate the possibility of serum miRNAs as biomarkers of lethal radiation injury. We found the specific expression of mmu-miR-374c-5p / mmu-miR-194-5p on first day and mmu-miR-192-5p / mmu-miR-223-3p on third day in the mouse serum only under 10 Gy irradiation by miRNA sequencing and all significantly correlated with lymphocyte counts by Pearson's correlation analysis. In addition, it was found that among the 4 candidate serum miRNAs, only highly-expressed mmu-miR-192-5p in mouse serum irradiated at lethal doses was returned to sham-like expression levels at 3 days post-irradiation with amifostine pretreatment and closely correlated with survival rate. We demonstrated for the first time that mmu-miR-192-5p screened from lethally irradiated mice sera can be used as a potential biomarker for lethal irradiation injury, which will be helpful to improve efficiency of medical treatment to minimize casualties after a large-scale nuclear accident.
在核或辐射事故中,需要快速识别那些暴露于潜在致死剂量照射下的人员。然而,现有的技术不足以对致死性损伤进行分类。一些研究已经探索了 miRNAs 作为电离辐射损伤生物标志物的潜力,然而,具有特定致死辐射损伤表达的 miRNAs 很少。因此,本研究旨在筛选和验证血清 miRNAs 作为致死性辐射损伤生物标志物的可能性。我们通过 miRNA 测序发现,在仅接受 10Gy 照射的小鼠血清中,mmu-miR-374c-5p/mmu-miR-194-5p 在第一天特异性表达,mmu-miR-192-5p/mmu-miR-223-3p 在第三天特异性表达,且均与淋巴细胞计数呈显著正相关(通过 Pearson 相关性分析)。此外,还发现,在 4 种候选血清 miRNAs 中,只有在致死剂量照射的小鼠血清中高度表达的 mmu-miR-192-5p 在接受氨磷汀预处理后 3 天的致死剂量照射后恢复到类似假照射的表达水平,且与存活率密切相关。我们首次证明,从致死性照射的小鼠血清中筛选出的 mmu-miR-192-5p 可作为潜在的致死照射损伤生物标志物,这有助于提高大规模核事故后医疗救治的效率,最大限度地减少伤亡。