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碳水化合物预饲后,对伴有失血性休克的多发伤的肝脏、肌肉、血清和尿液反应进行四室代谢组学分析。

A four-compartment metabolomics analysis of the liver, muscle, serum, and urine response to polytrauma with hemorrhagic shock following carbohydrate prefeed.

作者信息

Witowski Nancy, Lusczek Elizabeth, Determan Charles, Lexcen Daniel, Mulier Kristine, Ostrowski Beverly, Beilman Greg

机构信息

Department of Surgery, University of Minnesota, Minneapolis, MN, United States of America.

Minnesota NMR Center, University of Minnesota, Minneapolis, MN, United States of America.

出版信息

PLoS One. 2015 Apr 14;10(4):e0124467. doi: 10.1371/journal.pone.0124467. eCollection 2015.

Abstract

OBJECTIVE

Hemorrhagic shock accompanied by injury represents a major physiologic stress. Fasted animals are often used to study hemorrhagic shock (with injury). A fasted state is not guaranteed in the general human population. The objective of this study was to determine if fed animals would exhibit a different metabolic profile in response to hemorrhagic shock with trauma when compared to fasted animals.

METHODS

Proton (1H) NMR spectroscopy was used to determine concentrations of metabolites from four different compartments (liver, muscle, serum, urine) taken at defined time points throughout shock/injury and resuscitation. PLS-DA was performed and VIP lists established for baseline, shock and resuscitation (10 metabolites for each compartment at each time interval) on metabolomics data from surviving animals.

RESULTS

Fed status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The death rate for CPF animals is higher than FS animals (47 vs 28%). The majority of deaths occur post-resuscitation suggesting reperfusion injury. The metabolomics response to shock reflects priorities evident at baseline. FS animals raise the baseline degree of proteolysis to provide additional amino acids for energy production while CPF animals rely on both glucose and, to a lesser extent, amino acids. During early resuscitation levels of metabolites associated with energy production drop, suggesting diminished demand.

CONCLUSIONS

Feeding status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The response to shock reflects metabolic priorities at baseline.

摘要

目的

伴有损伤的失血性休克是一种主要的生理应激。禁食动物常被用于研究失血性休克(伴有损伤)。一般人群中无法保证处于禁食状态。本研究的目的是确定与禁食动物相比,喂食动物在遭受创伤性失血性休克时是否会表现出不同的代谢特征。

方法

使用质子(1H)核磁共振波谱法测定在休克/损伤及复苏过程中特定时间点采集的来自四个不同区室(肝脏、肌肉、血清、尿液)的代谢物浓度。对存活动物的代谢组学数据进行偏最小二乘判别分析(PLS-DA),并建立基线、休克和复苏阶段(每个时间间隔每个区室10种代谢物)的变量重要性投影(VIP)列表。

结果

在发生伴有损伤的失血性休克之前的喂食状态会改变这种创伤的代谢过程,并可能影响死亡率。对照饲料喂养(CPF)动物的死亡率高于禁食(FS)动物(47%对28%)。大多数死亡发生在复苏后,提示存在再灌注损伤。对休克的代谢组学反应反映了基线时明显的优先顺序。禁食动物提高蛋白水解的基线程度以提供额外的氨基酸用于能量产生,而对照饲料喂养动物则同时依赖葡萄糖,且在较小程度上依赖氨基酸。在早期复苏期间,与能量产生相关的代谢物水平下降,表明需求减少。

结论

在发生伴有损伤的失血性休克之前的喂食状态会改变这种创伤的代谢过程,并可能影响死亡率。对休克的反应反映了基线时的代谢优先顺序。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/864c/4396978/4910306dbaec/pone.0124467.g001.jpg

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