关键词: NPAS2 Rev-Erb-α circadian cycle glucose metabolism hypoxia

Mesh : Humans Pilot Projects Basic Helix-Loop-Helix Transcription Factors / blood Sleep Apnea, Obstructive / blood Male Nerve Tissue Proteins / blood Nuclear Receptor Subfamily 1, Group D, Member 1 / blood Middle Aged Female Circadian Rhythm / physiology Adult Hypoxia / blood Diabetes Mellitus, Type 2 / blood Polysomnography Case-Control Studies Blood Glucose / metabolism

来  源:   DOI:10.17219/dmp/185718

Abstract:
BACKGROUND: Obstructive sleep apnea (OSA) is one of the risk factors for diabetes mellitus type 2 (DM2). As OSA is associated with the disruption of the circadian rhythm, it affects circadian clock proteins, including neuronal PAS domain protein 2 (NPAS2) and nuclear receptor subfamily 1 group D member 1 (Rev-Erb-α). These proteins have been shown to be related to metabolic abnormalities, i.a., insulin resistance.
OBJECTIVE: The present pilot study aimed to investigate the NPAS2 and Rev-Erb-α protein serum levels in the groups of patients with severe OSA and severe OSA+DM2 in comparison with healthy controls, taking into account correlations with polysomnography (PSG) parameters (e.g., oxygen saturation (SpO2) variables).
METHODS: A total of 40 participants were included in the study. They were split into 3 groups as follows: the OSA group (n = 17; apnea-hypopnea index (AHI) >30, no DM2); the OSA+DM2 group (n = 7; AHI > 30 and DM2); and the control group (n = 16; AHI < 5, no DM2). All participants underwent a nocturnal PSG examination and had their blood collected the following morning. The serum levels of NPAS2 and Rev-Erb-α proteins were assessed using the enzyme-linked immunosorbent assay (ELISA).
RESULTS: The mean NPAS2 protein level was significantly lower in the OSA group as compared to healthy individuals (p = 0.017). Additionally, the OSA group presented with lower NPAS2 protein levels as compared to the OSA+DM2 group, but only a tendency was observed (p = 0.094). No differences in the Rev-Erb-α protein concentration were noticed. Furthermore, a negative correlation between AHI during rapid eye movement (REM) sleep and the NPAS2 protein serum level was observed (r = -0.478; p = 0.002).
CONCLUSIONS: Serum NPAS2 protein might be involved in metabolic dysregulation present among OSA patients, while the mechanism itself may be associated with REM sleep.
摘要:
背景:阻塞性睡眠呼吸暂停(OSA)是2型糖尿病(DM2)的危险因素之一。由于OSA与昼夜节律的破坏有关,它会影响生物钟蛋白质,包括神经元PAS结构域蛋白2(NPAS2)和核受体亚家族1组D成员1(Rev-Erb-α)。这些蛋白质已被证明与代谢异常有关,i.a.,胰岛素抵抗。
目的:本试验研究旨在研究重度OSA和重度OSA+DM2患者与健康对照组比较的NPAS2和Rev-Erb-α蛋白血清水平。考虑到与多导睡眠图(PSG)参数的相关性(例如,氧饱和度(SpO2)变量)。
方法:共有40名参与者被纳入研究。分为3组:OSA组(n=17;呼吸暂停低通气指数(AHI)>30,无DM2);OSADM2组(n=7;AHI>30和DM2);和对照组(n=16;AHI<5,无DM2)。所有参与者都接受了夜间PSG检查,并在第二天早上收集了血液。使用酶联免疫吸附测定(ELISA)评估NPAS2和Rev-Erb-α蛋白的血清水平。
结果:与健康个体相比,OSA组的平均NPAS2蛋白水平显着降低(p=0.017)。此外,与OSA+DM2组相比,OSA组的NPAS2蛋白水平较低,但只观察到一种趋势(p=0.094)。未观察到Rev-Erb-α蛋白浓度的差异。此外,观察到快速眼动(REM)睡眠期间的AHI与NPAS2蛋白血清水平之间呈负相关(r=-0.478;p=0.002)。
结论:血清NPAS2蛋白可能参与OSA患者的代谢失调,而机制本身可能与REM睡眠有关。
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