Rousseau Guillaume, Chao de la Barca Juan Manuel, Rougé-Maillart Clotilde, Teresiński Grzegorz, Jousset Nathalie, Dieu Xavier, Chabrun Floris, Prunier-Mirabeau Delphine, Simard Gilles, Reynier Pascal, Palmiere Cristian
Service de médecine légale et pénitentiaire, Centre Hospitalier Universitaire d'Angers, 49933, Angers Cedex 09, France.
Département de biochimie et génétique, Centre Hospitalier Universitaire d'Angers, 49933, Angers Cedex 09, France.
Int J Legal Med. 2019 May;133(3):889-898. doi: 10.1007/s00414-018-1937-y. Epub 2018 Sep 18.
Hypothermia is a potentially lethal condition whose postmortem diagnosis is often complex to perform due to the absence of pathognomonic lesions and biomarkers. Our first study of human serum and urinary metabolome in hypothermia fatalities sought novel biomarkers with better diagnostic performances than those already existing.
Thirty-two cases of hypothermia deaths and 16 cases excluding known antemortem exposure to cold or postmortem elements suggesting hypothermia were selected. A targeted metabolomic study allowing the detection and quantitation of 188 metabolites was performed on collected serum and urine using direct flow injection (FIA) and liquid chromatography (LC) separation, both coupled to tandem mass spectrometry (MS/MS). Amino acid quantification was also carried on using an in-house LC-MS/MS method in order to replicate the results obtained with the metabolomic study.
A discriminant metabolic signature allowing a clear separation between hypothermia and control groups was obtained in the serum. This signature was characterized by increased arginase activity and fatty acid unsaturation along with decreased levels of tryptophan in hypothermia fatalities compared to controls. By contrast, no discriminant metabolic signature separating hypothermia from control fatalities was found in urines.
The serum metabolic signature of hypothermia fatalities herein observed pointed toward metabolic adaptations that likely aimed at heat production enhancement, endothelial function, and cell membrane fluidity preservation. Novel biomarkers potentially useful in a hypothermia diagnosis were also identified.
体温过低是一种潜在的致命状况，由于缺乏特征性病变和生物标志物，其死后诊断往往很复杂。我们对体温过低死亡者的人血清和尿液代谢组进行的第一项研究，旨在寻找比现有生物标志物具有更好诊断性能的新型生物标志物。
选取32例体温过低死亡病例和16例排除已知生前暴露于寒冷或死后提示体温过低因素的病例。使用直接流动注射（FIA）和液相色谱（LC）分离，并结合串联质谱（MS/MS），对收集的血清和尿液进行靶向代谢组学研究，以检测和定量188种代谢物。还使用内部LC-MS/MS方法进行氨基酸定量，以复制代谢组学研究获得的结果。
在血清中获得了一种判别性代谢特征，可将体温过低组与对照组清晰区分开来。与对照组相比，这种特征的特点是体温过低死亡者中精氨酸酶活性增加、脂肪酸不饱和度增加以及色氨酸水平降低。相比之下，在尿液中未发现将体温过低与对照死亡者区分开来判别性代谢特征。
本文观察到的体温过低死亡者的血清代谢特征表明存在代谢适应性变化，这些变化可能旨在增强产热、维持内皮功能和细胞膜流动性。还鉴定出了可能对体温过低诊断有用的新型生物标志物。
