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基于 1H-NMR 和 UPLC-Q-TOF/MS 的血浆代谢组学整合研究鉴定大鼠弥漫性轴索损伤的生物标志物。

Integration of H NMR- and UPLC-Q-TOF/MS-based plasma metabonomics study to identify diffuse axonal injury biomarkers in rat.

机构信息

Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.

Faculty of Medical Technology, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China.

出版信息

Brain Res Bull. 2018 Jun;140:19-27. doi: 10.1016/j.brainresbull.2018.03.012. Epub 2018 Mar 29.

DOI:10.1016/j.brainresbull.2018.03.012
PMID:29605486
Abstract

Diffuse axonal injury (DAI) is much common during traumatic brain injury (TBI) and is associated with high mortality and poor neurological outcome. Although many studies have been examined, there are still no reliable objective diagnostic modalities available for clinicians to make an early diagnosis of DAI. Therefore, we established a rat model of DAI, applying an integrated H NMR- and UPLC-Q-TOF/MS-based metabonomics approach to identify differentially changed metabolites in plasma. A total of twenty-two metabolites in the injury group were identified as differentially changed. Among them, four metabolites, glutamine, pyruvate, glycerol and phosphocholine, were identified as candidate biomarkers based on their high fold-changes and biological functions, and may play important roles in axonal injury progression in DAI. Our study not only identified several novel biomarkers that improved our understanding of the metabolic events underlying DAI, but also may provide some potential novel therapeutic targets for preventing axonal injury in DAI.

摘要

弥漫性轴索损伤(DAI)在创伤性脑损伤(TBI)中更为常见,与高死亡率和不良神经预后相关。尽管已经进行了许多研究,但临床医生仍然没有可靠的客观诊断方法来早期诊断 DAI。因此,我们建立了 DAI 大鼠模型,应用整合的 H NMR 和 UPLC-Q-TOF/MS 代谢组学方法来鉴定血浆中差异变化的代谢物。在损伤组中鉴定出 22 种差异变化的代谢物。其中,根据其高倍数变化和生物学功能,谷氨酸、丙酮酸、甘油和磷酸胆碱这 4 种代谢物被鉴定为候选生物标志物,它们可能在 DAI 轴索损伤进展中发挥重要作用。我们的研究不仅鉴定了一些改善我们对 DAI 代谢事件理解的新型生物标志物,还可能为预防 DAI 中的轴索损伤提供一些潜在的新的治疗靶点。

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