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基于气相色谱-质谱联用技术在大鼠模型中对全身辐射后脑组织的早期代谢特征分析

Early metabolic characterization of brain tissues after whole body radiation based on gas chromatography-mass spectrometry in a rat model.

作者信息

Yao Xueting, Xu Chao, Cao Yurong, Lin Lin, Wu Hanxu, Wang Chang

机构信息

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou, P. R. China.

出版信息

Biomed Chromatogr. 2019 Mar;33(3):e4448. doi: 10.1002/bmc.4448. Epub 2018 Dec 26.

Abstract

Radiation-induced brain injury involves acute, early delayed and late delayed damage based on the time-course and clinical manifestations. The acute symptoms are mostly transient and reversible, whereas the late delayed radiation-induced changes are progressive and irreversible. Therefore, evaluation of the organ-specific early response to ionizing radiation exposure is necessary for improving treatment strategies and minimizing possible damage at an early stage after radiation exposure. In the current study, the gas chromatography-mass spectrometry technique based on metabolomics coupled with metabolic correlation network was applied to investigate the early metabolic characterization of rat brain tissues following irradiation. Our findings showed that the metabolic response to irradiation was not just limited to the variations of individual metabolite levels, but also accompanied by alterations of network correlations among various metabolites. Metabolite clustering indicated that energy metabolism disorder and inflammation response were induced following radiation exposure. The correlation networks revealed that the strong positive correlations of differential metabolites were highly reduced and significant negative linkages were highlighted in irradiated groups even without statistical changes in metabolic levels. Our findings provided new insights into our understanding of the radiation-induced acute brain injury mechanism and clues as to the therapy target for clinical applications.

摘要

基于时间进程和临床表现,辐射诱导的脑损伤包括急性、早期延迟和晚期延迟损伤。急性症状大多是短暂且可逆的,而晚期延迟辐射诱导的变化是渐进且不可逆的。因此,评估器官对电离辐射暴露的特异性早期反应对于改进治疗策略以及在辐射暴露后的早期阶段将可能的损伤降至最低是必要的。在当前研究中,基于代谢组学并结合代谢相关网络的气相色谱 - 质谱技术被用于研究大鼠脑组织在辐照后的早期代谢特征。我们的研究结果表明,对辐照的代谢反应不仅限于个别代谢物水平的变化,还伴随着各种代谢物之间网络相关性的改变。代谢物聚类表明,辐射暴露后会诱导能量代谢紊乱和炎症反应。相关网络显示,即使代谢水平没有统计学变化,辐照组中差异代谢物的强正相关性也大幅降低,显著的负相关性则凸显出来。我们的研究结果为理解辐射诱导的急性脑损伤机制提供了新的见解,并为临床应用的治疗靶点提供了线索。

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