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基于靶向脂质组学分析的大鼠血浆中急性辐射暴露后早期分诊和剂量估计的脂质筛选。

Screening of Lipids for Early Triage and Dose Estimation after Acute Radiation Exposure in Rat Plasma Based on Targeted Lipidomics Analysis.

机构信息

China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, P. R. China.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

J Proteome Res. 2021 Jan 1;20(1):576-590. doi: 10.1021/acs.jproteome.0c00560. Epub 2020 Nov 17.

Abstract

Rapid early triage and dose estimation is vital for limited medical resource allocation and treatment of a large number of the wounded after radiological accidents. Lipidomics has been utilized to delineate biofluid lipid signatures after irradiation. Here, high-coverage targeted lipidomics was employed to screen radiosensitive lipids after 0, 1, 2, 3, 5, and 8 Gy total body irradiation at 4, 24, and 72 h postirradiation in rat plasma. Ultra-performance liquid chromatography-tandem mass spectrometry with a multiple reaction monitoring method was utilized. In total, 416 individual lipids from 18 major classes were quantified and those biomarkers altered in a dose-dependent manner constituted panel A-panel D. Receiver operator characteristic curve analysis using combined lipids showed good to excellent sensitivity and specificity in triaging different radiation exposure levels (area under curve = 0.814-1.000). The equations for dose estimation were established by stepwise regression analysis for three time points. A novel strategy for radiation early triage and dose estimation was first established and validated using panels of lipids. Our study suggests that it is feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage, which can provide further insights in developing lipidomics strategies for radiation biodosimetry in humans.

摘要

快速的早期分诊和剂量估计对于有限的医疗资源分配和大量伤员的治疗至关重要。脂质组学已被用于描绘放射事故后生物体液的脂质特征。在这里,我们采用高覆盖度的靶向脂质组学方法,在大鼠血浆中分别于照射后 0、1、2、3、5 和 8Gy,4、24 和 72h 时筛选出全身照射后敏感的脂质。采用超高效液相色谱-串联质谱法(多重反应监测法)进行检测。共定量了 18 个主要脂质类别的 416 种脂质,这些随剂量变化而改变的生物标志物构成了 panel A-panel D。采用联合脂质的受试者工作特征曲线分析显示,不同辐射暴露水平的分诊具有良好到极好的敏感性和特异性(曲线下面积=0.814-1.000)。通过逐步回归分析,针对三个时间点建立了剂量估算方程。本研究首次建立并验证了使用脂质组学 panel 进行辐射早期分诊和剂量估计的新策略。我们的研究表明,使用靶向脂质组学平台获取定量脂质生物标志物 panel 进行快速、高通量分诊是可行的,这为开发人类辐射生物剂量学的脂质组学策略提供了进一步的思路。

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