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高通量靶向脂质组学筛选大鼠血浆放射性胃肠损伤生物标志物。

Screening of radiation gastrointestinal injury biomarkers in rat plasma by high-coverage targeted lipidomics.

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, China.

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

出版信息

Biomarkers. 2022 Jul;27(5):448-460. doi: 10.1080/1354750X.2022.2056920. Epub 2022 Apr 4.

Abstract

INTRODUCTION

In the event of radiological accidents and cancer radiotherapies in the clinic, the gastrointestinal (GI) system is vulnerable to ionizing radiation and shows GI injury. Accessible biomarkers may provide means to predict, evaluate, and treat GI tissue damage. The current study investigated radiation GI injury biomarkers in rat plasma.

MATERIAL AND METHODS

High-coverage targeted lipidomics was employed to profile lipidome perturbations at 72 h after 0, 1, 2, 3, 5, and 8 Gy (Co γ-rays at 1 Gy/min) total-body irradiation in male rat jejunum. The results were correlated with previous plasma screening outcomes.

RESULTS

In total, 93 differential metabolites and 28 linear dose-responsive metabolites were screened in the jejunum. Moreover, 52 lipid species with significant differences both in jejunum and plasma were obtained. Three lipid species with linear dose-response relationship both in jejunum and plasma were put forth, which exhibited good to excellent sensitivity and specificity in triaging different exposure levels.

DISCUSSION

The linear dose-effect relationship of lipid metabolites in the jejunum and the triage performance of radiation GI injury biomarkers in plasma were studied for the first time.

CONCLUSION

The present study can provide insights into expanded biomarkers of IR-mediated GI injury and minimally invasive assays for evaluation.

摘要

简介

在临床放射事故和癌症放射治疗中,胃肠道(GI)系统容易受到电离辐射的影响,并表现出 GI 损伤。可及的生物标志物可能为预测、评估和治疗 GI 组织损伤提供手段。本研究探讨了大鼠血浆中辐射性 GI 损伤的生物标志物。

材料与方法

采用高覆盖率靶向脂质组学技术,在雄性大鼠空肠接受 0、1、2、3、5 和 8Gy(Coγ射线,1Gy/min)全身照射后 72h 时,对脂质组进行分析,以确定脂质组的变化。将结果与之前的血浆筛选结果进行关联。

结果

共筛选出 93 种差异代谢物和 28 种线性剂量反应代谢物。此外,还获得了在空肠和血浆中均有显著差异的 52 种脂质种类。提出了在空肠和血浆中均具有线性剂量反应关系的 3 种脂质种类,它们在甄别不同暴露水平方面具有良好到极好的敏感性和特异性。

讨论

首次研究了空肠中脂质代谢物的线性剂量效应关系以及血浆中辐射性 GI 损伤生物标志物的甄别性能。

结论

本研究可为 IR 介导的 GI 损伤的扩展生物标志物和评估的微创检测提供参考。

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