| 代清池,习聪,闫宇康,等.大鼠血浆非靶向代谢组学筛选及其验证[J].中华放射医学与防护杂志,2026,46(6):555-563.Dai Qingchi,Xi Cong,Yan Yukang,et al.Untargeted metabolomics-based selection and validation of radiation-sensitive metabolites in rat plasma[J].Chin J Radiol Med Prot,2026,46(6):555-563 |
| 大鼠血浆非靶向代谢组学筛选及其验证 |
| Untargeted metabolomics-based selection and validation of radiation-sensitive metabolites in rat plasma |
| 投稿时间：2025-12-24 |
| DOI：10.3760/cma.j.cn112271-20251224-00445 |
| 中文关键词: 电离辐射|非靶向代谢组学|绝对定量|生物标志物|代谢通路 |
| 英文关键词:Ionizing radiation|Untargeted metabolomics|Absolute quantification|Biomarker|Metabolic pathway |
| 基金项目:国家自然科学基金(82003393);中国疾控中心辐射安全所青年科学研究所长基金(2023-02) |
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| 中文摘要: |
| 目的 筛选与初步验证全身照射大鼠血浆中的辐射敏感代谢物,为辐射生物标志物研究提供实验依据。方法 建立60Co γ射线全身照射大鼠模型,剂量点为0、4、8、12 Gy,照射后6 h采血。采用非靶向代谢组学进行0 Gy和4、8、12 Gy组的差异代谢物筛选及通路富集分析。进一步确定稳定的差异代谢物,采用靶向绝对定量验证。结果 非靶向分析共鉴定出323个差异代谢物,主要富集于嘧啶代谢等通路。结合文献筛选,确定牛磺酸、己酰肉碱及丁酰肉碱3种代谢物为稳定候选代谢物。靶向绝对定量结果显示,3种代谢物变化趋势与非靶向一致,且牛磺酸呈剂量依赖性上调,拟合剂量-效应模型y = 2.337x+37.54(F = 6.76,P < 0.05)。牛磺酸、己酰肉碱及丁酰肉碱在区分0 Gy与>0 Gy照射组时均表现出良好的分类准确性(AUC > 0.7)。结论 大鼠受到全身照射后6 h血浆代谢物发生显著变化,牛磺酸、己酰肉碱及丁酰肉碱作为辐射敏感代谢物较稳定,其中牛磺酸具有良好的剂量-效应关系。非靶向筛选与靶向绝对定量验证相结合可提高辐射生物标志物发现的可靠性。 |
| 英文摘要: |
| Objective To select and preliminarily validate radiation-sensitive metabolites in the plasma of rats exposed to total-body irradiation (TBI), aiming to provide an experimental basis for research on radiation biomarkers. Methods Models of rats subjected to TBI were established using 60Co γ-rays at doses of 0, 4, 8, and 12 Gy. Plasma samples were then collected from these rats at 6 h post-irradiation. Using untargeted metabolomics, differential metabolites were selected from the plasma samples, followed by pathway enrichment analysis. Stable metabolites were then identified and validated using the targeted absolute quantification. Results A total of 323 differential metabolites were identified through untargeted analysis, and they were primarily enriched in pathways such as pyrimidine metabolism. In combination with a literature review, three stable candidate metabolites were selected: taurine, hexanoylcarinitine, and butyrylcarnitine. Targeted absolute quantification result indicate that the three metabolites followed trends consistent with those observed in the untargeted analysis. Among these, taurine exhibited a dose-dependent upregulation, and the fitted dose-effect model was y = 2.337x + 37.54 (F = 6.76, P < 0.05). These metabolites all demonstrated high classification accuracy (AUC > 0.7) in discriminating between the 0 Gy and > 0 Gy irradiation groups. Conclusions Metabolites in rat plasma change significantly at 6 h post-TBI. As radiation-sensitive metabolites, taurine, hexanoylcarnitine, and butyrylcarnitine are relatively stable. Notably, taurine exhibits a clear dose-effect relationship. The combination of untargeted metabolomics-based selection and validation using targeted absolute quantification offers a reliable method for identifying radiation biomarkers. |
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