Sleep Unit, Department of Respiratory Medicine, Reina Sofia University Hospital, Cordoba, Spain.
J Sleep Res. 2012 Apr;21(2):139-46. doi: 10.1111/j.1365-2869.2011.00955.x. Epub 2011 Sep 17.
To examine whether differentially expressed proteins are present in the serum of patients with obstructive sleep apnoea (OSA), iTRAQ techniques (isobaric tags for relative and absolute quantification) were employed in a prospective study. Individuals were assigned to either a non-OSA control group (apnoea-hypopnoea index, AHI <5) or an OSA group (AHI ≥5). Blood samples were collected, aliquoted and frozen at -80 °C. Protein digestion and tagging with iTRAQ4plex® and mass spectrometry analysis was then performed (MALDI TOF/TOF). Ten male subjects were included in the control group (age = 45 ± 9.7 years) and 30 male patients in the OSA group (age = 45 ± 10.7 years), the latter being then subdivided into three severity groups. A total of 103 proteins were identified with differential levels between patients with OSA and controls. Of these, 11 proteins were underexpressed and 19 were overexpressed in patients with OSA. C4BPA and thrombospondin were underexpressed in all three OSA severity groups. Among the overexpressed proteins, 13 were overexpressed in the mild OSA group, seven in the moderate group and five in the severe group. Analysis of interactions between the identified proteins revealed that protein alterations in OSA are primarily associated with derangements in lipid and vascular metabolic pathways. This study provides initial evidence that differential protein expression occurs in adults with OSA, and that such proteins change according to disease severity, and appear to primarily involve lipid and vascular metabolic pathways.
为了研究阻塞性睡眠呼吸暂停(OSA)患者的血清中是否存在差异表达蛋白,我们采用 iTRAQ 技术(相对和绝对定量的同位素标记)进行了一项前瞻性研究。将个体分为非 OSA 对照组(呼吸暂停低通气指数,AHI<5)或 OSA 组(AHI≥5)。采集血液样本,等分并在-80°C 下冷冻。然后进行蛋白质消化和 iTRAQ4plex®标记以及质谱分析(MALDI TOF/TOF)。10 名男性受试者纳入对照组(年龄=45±9.7 岁),30 名男性患者纳入 OSA 组(年龄=45±10.7 岁),后者随后再分为三个严重程度组。在 OSA 患者和对照组之间共鉴定出 103 种具有差异水平的蛋白质。其中,11 种蛋白在 OSA 患者中表达下调,19 种蛋白表达上调。C4BPA 和血栓素在所有三个 OSA 严重程度组中均表达下调。在表达上调的蛋白中,13 种在轻度 OSA 组中表达上调,7 种在中度组中表达上调,5 种在重度组中表达上调。对鉴定出的蛋白质之间的相互作用进行分析发现,OSA 中的蛋白质改变主要与脂质和血管代谢途径的紊乱有关。这项研究首次提供了证据,表明 OSA 患者存在差异蛋白表达,并且这些蛋白根据疾病严重程度而变化,似乎主要涉及脂质和血管代谢途径。