Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia; Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
Biochim Biophys Acta Mol Basis Dis. 2020 Jan 1;1866(1):165572. doi: 10.1016/j.bbadis.2019.165572. Epub 2019 Oct 29.
Bronchial asthma is one of the most common, chronic respiratory diseases, characterized by reversible airway obstruction, eosinophil and Th2 infiltration, airway hyperresponsiveness and airway remodelling; with many cells and mediators involved. Metabolomics is a relatively new field in "omics" sciences enabling the identification of metabolome for better diagnostics and studying of diseases phenotype. The aim of this study was to investigate the role of targeted metabolomics study for better understanding of the bronchial asthma pathophysiology and finding potential biomarkers in experimental models of eosinophilic inflammation. Plasma level of 185 metabolites was measured with the AbsoluteIDQ™ p180 kit in guinea pigs with experimentally-induced allergic inflammation (n = 15) compared to naïve non-sensitised and non-challenged controls (n = 18). Of the 185 metabolites identified in plasma, 22 were significantly different and changed in ovalbumin sensitised animals. Plasma level of 13 phosphatidylcholines with saturated and unsaturated long-chain fatty acids, total phosphatidylcholines count, carnitine, symmetric dimethylarginine and its ratio to total unmodified arginine, and kynurenine to tryptophan ratio were found to be decreased, while phospholipase A2 activity indicator, tryptophan, taurine and ratio of methionine sulfoxide to unmodified methionine were found to be increased in sensitised guinea pigs compared to naïve controls. Targeted metabolomic analysis revealed significant differences in plasma metabolome of sensitised guinea pigs. Our observations point to the activation of inflammatory and immune pathways, as well as the involvement of oxidative stress.
支气管哮喘是最常见的慢性呼吸道疾病之一，其特征为可逆性气道阻塞、嗜酸性粒细胞和 Th2 浸润、气道高反应性和气道重塑；涉及多种细胞和介质。代谢组学是“组学”科学中一个相对较新的领域，能够识别代谢组，从而更好地进行诊断和研究疾病表型。本研究旨在通过靶向代谢组学研究来探讨支气管哮喘发病机制，并在嗜酸性粒细胞炎症的实验模型中寻找潜在的生物标志物。本研究使用 AbsoluteIDQ™ p180 试剂盒测量了 15 只实验性变应性炎症的豚鼠与 18 只未致敏非挑战对照之间的 185 种代谢物的血浆水平。在鉴定的 185 种血浆代谢物中，有 22 种明显不同，并且在卵清蛋白致敏动物中发生了变化。发现 13 种带有饱和和不饱和长链脂肪酸的磷脂酰胆碱、总磷脂酰胆碱计数、肉碱、对称二甲基精氨酸及其与总未修饰精氨酸的比值、以及犬尿氨酸与色氨酸的比值降低，而磷脂酶 A2 活性指标、色氨酸、牛磺酸和甲硫氨酸氧化物与未修饰甲硫氨酸的比值在致敏豚鼠中升高与未致敏对照相比。靶向代谢组学分析显示致敏豚鼠的血浆代谢组存在显著差异。我们的观察结果表明炎症和免疫途径的激活，以及氧化应激的参与。
