Urinary metabolic network analysis in trauma, hemorrhagic shock, and resuscitation
Urinary metabolic network analysis in trauma, hemorrhagic shock, and resuscitation
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DOI：
10.1007/s11306-012-0441-5
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发表时间：
2013-02-01
期刊：
影响因子：
3.6
通讯作者：
Beilman, Greg
中科院分区：
文献类型：
--
作者：
Lusczek, Elizabeth R.;Lexcen, Daniel R.;Beilman, Greg
出血性休克，通常是创伤性损伤的结果，是一种灌注减少的状况，导致向组织输送的氧气减少。由缺血（减少的氧递送）和再灌注（氧递送的恢复）诱导的氧递送的中断对细胞代谢和体内平衡的维持具有深远的影响。用尺度不变的代谢网络研究创伤和失血性休克的病理生理状态。根据在出血性休克猪模型（包括肺挫伤、肝挤压伤和35%受控出血）中设定时间点收集的尿样的NMR光谱构建尿代谢谱。该网络是根据这些代谢谱构建的。偏最小二乘判别分析（PLS-DA）模型，区分实验时间点也被构建。网络（代谢物之间的功能关系）和PLS-DA模型（可观察到的实验时间过程的关系）的比较显示了互补的信息。首先，缺血/再灌注损伤和出血导致的细胞死亡证据与早期复苏时间点相关。第二，蛋白质代谢增加和创伤性损伤的证据与复苏时间点晚有关。这些结果与休克代谢进展的普遍接受的观点是一致的。
Hemorrhagic shock, often a result of traumatic injury, is a condition of reduced perfusion that results in diminished delivery of oxygen to tissues. The disruption in oxygen delivery induced by both ischemia (diminished oxygen delivery) and reperfusion (restoration of oxygen delivery) has profound consequences for cellular metabolism and the maintenance of homeostasis. The pathophysiologic state associated with traumatic injury and hemorrhagic shock was studied with a scale-invariant metabolic network. Urinary metabolic profiles were constructed from NMR spectra of urine samples collected at set timepoints in a porcine model of hemorrhagic shock that included a pulmonary contusion, a liver crush injury, and a 35 % controlled bleed. The network was constructed from these metabolic profiles. A partial least squares discriminant analysis (PLS-DA) model that discriminates by experimental timepoint was also constructed. Comparisons of the network (functional relationships among metabolites) and PLS-DA model (observable relationships to experimental time course) revealed complementary information. First, ischemia/reperfusion injury and evidence of cell death due to hemorrhage was associated with early resuscitation timepoints. Second, evidence of increased protein catabolism and traumatic injury was associated with late resuscitation timepoints. These results are concordant with generally accepted views of the metabolic progression of shock.