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病理代谢:严重创伤患者血浆代谢组的探索性研究

Pathologic metabolism: an exploratory study of the plasma metabolome of critical injury.

作者信息

Peltz Erik D, D'Alessandro Angelo, Moore Ernest E, Chin Theresa, Silliman Christopher C, Sauaia Angela, Hansen Kirk C, Banerjee Anirban

机构信息

From the Departments of Surgery/Trauma Research Center (E.D.P., E.E.M., T.C., A.B., C.C.S.), Biochemistry and Molecular Genetics (A.D., K.C.H.), and Health Care Policy and Research (A.S.), Anschutz Medical Campus, and Department of Pediatrics-Haematology/Oncology (C.C.S.), Anschutz Medical Campus-Children's Hospital Colorado, School of Medicine, University of Colorado Denver; and Department of Surgery (E.E.M.), Denver Health Medical Center, Aurora; and Belle Bonfils Blood Center (C.C.S.), Denver Colorado.

出版信息

J Trauma Acute Care Surg. 2015 Apr;78(4):742-51. doi: 10.1097/TA.0000000000000589.

Abstract

BACKGROUND

Severe trauma is associated with massive alterations in metabolism. Thus far, investigations have relied on traditional bioanalytic approaches including calorimetry or nuclear magnetic resonance. However, recent strides in mass spectrometry (MS)-based metabolomics present enhanced analytic opportunities to characterize a wide range of metabolites in the critical care setting.

METHODS

MS-based metabolomics analyses were performed on plasma samples from severely injured patients' trauma activation field blood and plasma samples obtained during emergency department thoracotomy. These were compared against the metabolic profiles of healthy controls.

RESULTS

Few significant alterations were observed between trauma activation field blood and emergency department thoracotomy patients. In contrast, we identified trauma-dependent metabolic signatures, which support a state of hypercatabolism, driven by sugar consumption, lipolysis and fatty acid use, accumulation of ketone bodies, proteolysis and nucleoside breakdown, which provides carbon and nitrogen sources to compensate for trauma-induced energy consumption and negative nitrogen balance. Unexpectedly, metabolites of bacterial origin (including tricarballylate and citramalate) were detected in plasma from trauma patients.

CONCLUSION

In the future, the correlation between metabolomics adaptation and recovery outcomes could be studied by MS-based approaches, and this work can provide a method for assessing the efficacy of alternative resuscitation strategies.

摘要

背景

严重创伤与代谢的巨大改变有关。到目前为止,研究依赖于传统的生物分析方法,包括量热法或核磁共振。然而,基于质谱(MS)的代谢组学的最新进展为在重症监护环境中表征广泛的代谢物提供了更好的分析机会。

方法

对严重受伤患者创伤激活现场血液的血浆样本以及急诊开胸手术期间获得的血浆样本进行基于MS的代谢组学分析。将这些样本与健康对照的代谢谱进行比较。

结果

在创伤激活现场血液和急诊开胸手术患者之间观察到很少有显著变化。相比之下,我们确定了创伤依赖的代谢特征,这支持一种高分解代谢状态,由糖消耗、脂肪分解和脂肪酸利用、酮体积累、蛋白质水解和核苷分解驱动,这些过程提供碳和氮源以补偿创伤引起的能量消耗和负氮平衡。出乎意料的是,在创伤患者的血浆中检测到了细菌来源的代谢物(包括三羧甲基戊酸和柠苹酸)。

结论

未来,可以通过基于MS的方法研究代谢组学适应性与恢复结果之间的相关性,这项工作可以为评估替代复苏策略的疗效提供一种方法。

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