儿童严重脓毒症和全身炎症反应综合征与先天免疫激素炎症反应及氨基酸动力学相关的代谢和生物能纵向特征。

Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children.

机构信息

Pediatric Intensive Care Unit, University Hospital, Medical School, University of Crete, Heraklion, Greece.

Pediatric Hematology - Oncology, Medical School, University of Crete, Heraklion, Greece.

出版信息

JPEN J Parenter Enteral Nutr. 2018 Aug;42(6):1061-1074. doi: 10.1002/jpen.1050. Epub 2018 Jan 16.

DOI:10.1002/jpen.1050

PMID:29338093

Abstract

BACKGROUND

Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis.

METHODS

Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX.

RESULTS

Resistin, eHSP72, eHSP90α, and nitrate were longitudinally higher in sepsis compared with SIRS (p<0.05); mHSP72, nHSP72, VO , VCO , EE, and metabolic pattern were repressed in sepsis compared with SIRS (p<0.05). Septic patients had lower ATP and TBARS compared with controls on day 1, lower ATP compared with SIRS on day 3 (p<0.05), but higher levels of BVR activity. Sepsis exhibited higher phenylalanine levels on day 1, serine on day 3; lower glutamine concentrations on days 3 and 5 (p<0.05). Resistin, inversely related to ATP, was independently associated with sepsis, along with mHSP72 and eHSP90α (p<0.05); TBARS and VO were independently associated with organ failure (p<0.05)). Septic nonsurvivors had malnutrition, persistently repressed metabolism, mHSP72, and induced resistin and adiponectin (p<0.05).

CONCLUSIONS

A pattern of early longitudinal induction of metabolic-hormones and eHSP72/HSP90α, repression of bioenergetics and innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased resistin and adiponectin are associated with poor outcome.

摘要

背景

实验数据表明脓毒症会影响线粒体功能和代谢。我们旨在研究脓毒症患儿的能量代谢、代谢、激素、氨基酸和固有免疫的纵向变化。

方法

纳入 68 名儿童（脓毒症 18 例，全身炎症反应综合征[SIRS]23 例，健康对照 27 例）。采用高效液相色谱法（HPLC）测定血浆氨基酸水平；采用流式细胞术以单核细胞（m）和中性粒细胞（n）热休克蛋白（HSP）水平的平均荧光强度（MFI）表示；通过酶联免疫吸附试验（ELISA）评估抵抗素、脂联素和细胞外（e）HSP 水平；用荧光素酶发光法测定白细胞中的 ATP 水平；用比色法测定脂质过氧化产物（TBARS）；用化学发光法测定亚硝酸盐和硝酸盐水平；用酶法测定胆红素还原酶（BVR）活性；用 E-COVX 测定能量消耗（EE）。

结果

与 SIRS 相比，脓毒症患者的抵抗素、eHSP72、eHSP90α 和硝酸盐水平呈纵向升高（p<0.05）；与 SIRS 相比，脓毒症患者的 mHSP72、nHSP72、VO、VCO、EE 和代谢模式受到抑制（p<0.05）。与对照组相比，脓毒症患者第 1 天的 ATP 和 TBARS 水平较低，第 3 天的 ATP 水平较低（与 SIRS 相比，p<0.05），但 BVR 活性较高。脓毒症患者第 1 天的苯丙氨酸水平较高，第 3 天的丝氨酸水平较高；第 3 天和第 5 天的谷氨酰胺浓度较低（p<0.05）。抵抗素与 ATP 呈负相关，与 mHSP72 和 eHSP90α 一起与脓毒症独立相关（p<0.05）；TBARS 和 VO 与器官衰竭独立相关（p<0.05））。脓毒症非幸存者存在营养不良、持续抑制代谢、mHSP72 和诱导抵抗素和脂联素（p<0.05）。