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实验性自身免疫性心肌炎大鼠模型中的尿候选生物标志物。

Urinary candidate biomarkers in an experimental autoimmune myocarditis rat model.

机构信息

Department of Laboratory Medicine, Beijing Hospital, National Center of Gerontology, Beijing, China; Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

出版信息

J Proteomics. 2018 May 15;179:71-79. doi: 10.1016/j.jprot.2018.02.032. Epub 2018 Mar 7.

Abstract

UNLABELLED

Urine is a better source than plasma for biomarker studies, as it can accumulate all changes in the body. Various candidate urinary biomarkers of physiological condition, kidney disease and even brain dysfunction, have been detected in urine; however, urine has rarely been used to reflect cardiac diseases. In this study, urine at day 0, 14, 21 and 28 were collected from the myosin-induced autoimmune myocarditis rat models. The candidate urinary biomarkers were then characterized using the isobaric tandem mass tag labeling approach coupled with offline two-dimensional reverse-phase liquid chromatography and high-resolution mass spectrometry. Compared with controls, forty-six urinary proteins were significantly changed in the myocarditis rats; among them, ten had previously been associated with myocarditis, twelve corresponding gene products had annotated as mainly cardiovascular network genes by the Ingenuity Pathway Analysis, four urinary proteins were validated by western blot, thirteen were reported in previous urine proteome studies of other diseases and twenty-six were reported the first time to be related to myocarditis.

SIGNIFICANCE

This is the first study to use isobaric tandem mass tag labeling approach in the urine proteome analysis of experimental autoimmune myocarditis. These findings may provide clues for the pathogenesis of myocarditis. And the study showed that urine can be a good source of myocarditis biomarkers.

摘要

未标记

尿液是生物标志物研究的比血浆更好的来源,因为它可以积累体内的所有变化。已经在尿液中检测到各种候选尿液生物标志物,包括生理状况、肾脏疾病甚至脑功能障碍;然而,尿液很少用于反映心脏疾病。在这项研究中,从肌球蛋白诱导的自身免疫性心肌炎大鼠模型中收集了第 0、14、21 和 28 天的尿液。然后使用等重串联质量标签标记方法结合离线二维反相液相色谱和高分辨率质谱对候选尿液生物标志物进行了表征。与对照组相比,在心肌炎大鼠中,有 46 种尿液蛋白明显改变;其中,有 10 种先前与心肌炎有关,12 种相应的基因产物通过 IPA 被注释为主要心血管网络基因,4 种尿液蛋白通过 Western blot 进行了验证,13 种在其他疾病的尿液蛋白质组学研究中有报道,26 种是首次报道与心肌炎有关。

意义

这是首次使用等重串联质量标签标记方法在实验性自身免疫性心肌炎的尿液蛋白质组学分析中进行的研究。这些发现可能为心肌炎的发病机制提供线索。该研究表明,尿液可以作为心肌炎生物标志物的良好来源。

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