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急性肺损伤炎症反应失控所致的系统代谢紊乱及其发生机制

Systemic metabolic changes caused by inflammation progression in patients with acute lung injury

  • 摘要:
    目的 探讨炎症反应失控致肺损伤患者的代谢改变情况。
    方法 采用核磁共振波谱仪(NMR)检测创伤致全身性炎症反应综合征(SIRS)、急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)患者的血清NMR氢谱,进行整体代谢组分析。
    结果 NMR谱的偏最小二乘法-判别分析(PLS-DA)可区分SIRS患者在发生ALI、甚至ARDS后的代谢模式迁移过程。SIRS患者以低化学位移区段的信号增强为主,主要包含酪氨酸、赖氨酸等生酮氨基酸谱峰;ALI/ARDS患者则以δ1.02~2.50和δ3.02~4.14积分区段信号增强为主,主要包含乳酸、缬氨酸、精氨酸、谷氨酸等多种生糖氨基酸,以及丙酮酸、肌酸、脂质的脂肪酸、甘油等谱峰。代谢通路富集显示,ALI/ARDS的发生主要与糖酵解、糖异生、丙酮酸代谢、甘油酯代谢、精氨酸代谢、初级胆汁酸合成等通路的激活有关,提示ALI炎症反应失控所致的系统代谢紊乱以缺氧状态下高分解代谢为特征。
    结论 血清整体代谢组能够反映肺损伤后患者的代谢改变,进而有助于监测炎症反应失控导致肺损伤的进程,以及阐明肺损伤代谢紊乱发生的分子机制。

     

    Abstract:
    Objective To analyze the systemic metabolic changes of patients with uncontrolled inflammation response after acute lung injury (ALI) happened.
    Methods Traumatic patients with systemic inflammatory response syndrome (SIRS), ALI and acute respiratory distress syndrome (ARDS) were selected as subjects, the serum 1H-NMR spectra were recorded on a Varian Unity INOVA-600 spectrometer and analyzed by pattern recognition analyses.
    Results The partial least squares-discriminant analysis (PLS-DA) could distinguish the migration process of metabolic patterns from SIRS to ALI and even ARDS. Corresponding metabolite assignment indicated that NMR profiles responsible for SIRS discrimination were distributed in low chemical shift regions, mainly composed of ketogenic amino acids such as tyrosine and lysine, while δ1.02-2.50 and δ3.02-4.14 integral regions for ALI/ARDS patients, principally consisted of various proton signals of lactate, valine, arginine, glutamic acid, and other glycogenic amino acids, pyruvate, creatine, along with fatty acyl chains and glycerol backbone of lipids. Pathway enrichment analyses of metabolites revealed the occurrence of ALI/ARDS were mainly related to the activation of glycolysis, gluconeogenesis, pyruvate metabolism, glyceride metabolism, arginine metabolism, and primary bile acid synthesis. This result indicates that the systemic metabolic disorder of patients with acute lung injury caused by uncontrolled inflammatory response was characterized by hypercatabolism under hypoxia.
    Conclusions The serum NMR-based metabonomic profiles could reflect the overall metabolic changes of patients after lung damage, which will contribute to surveillance and elucidation mechanism of ALI/ARDS.

     

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