Moreira Susana, Rodrigues Raquel, Barros André B, Pejanovic Nadja, Neves-Costa Ana, Pedroso Dora, Pereira Cláudia, Fernandes Dina, Rodrigues João Valença, Barbara Cristina, Moita Luís Ferreira
Departamento de Pneumologia, Centro Hospitalar Lisboa Norte, EPE, Lisboa, Portugal.
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Front Med (Lausanne). 2017 Nov 6;4:187. doi: 10.3389/fmed.2017.00187. eCollection 2017.
Metabolic syndrome and cardiovascular disease are strongly associated with obstructive sleep apnea syndrome (OSAS), which causes substantial changes to normal circadian physiological functions, including metabolic pathways. Because core clock genes are known to be modulated by sleep/vigilance cycles, we asked whether the expression level of mRNA coding for clock genes is altered in non-treated OSAS patients and if it can be corrected by standard continuous positive airway pressure (CPAP) treatment.
Peripheral blood was collected from male patients diagnosed with severe OSAS (apnea-hypopnea index ≥ 30/h) before and after treatment initiation. qPCR was used to measure mRNA levels of genes associated with the central circadian pacemaker including , and three genes () in peripheral blood mononuclear cells (PBMCs).
We found statistically significant differences for (-value = 0.022) expression in PBMCs of OSAS patients which were not reverted by treatment with CPAP. We have also found a substantial decrease in the slow wave sleep (SWS) content in OSAS patients (-value < 0.001) that, contrary to REM sleep, was not corrected by CPAP (-value = 0.875).
CPAP treatment does not correct substantial changes in expression of core clock genes in OSAS patients. Because CPAP treatment is also unable to normalize the SWS in these patients, it is likely that additional therapeutic interventions that increase SWS content and complement the benefits of CPAP are required to more effectively reduce the known increased cardiovascular risk associated with OSAS patients.
代谢综合征和心血管疾病与阻塞性睡眠呼吸暂停综合征(OSAS)密切相关,OSAS会导致正常昼夜生理功能发生重大变化,包括代谢途径。由于已知核心生物钟基因受睡眠/警觉周期调节,我们探究了未经治疗的OSAS患者中编码生物钟基因的mRNA表达水平是否改变,以及标准持续气道正压通气(CPAP)治疗能否纠正这种改变。
在治疗开始前和治疗后,从诊断为重度OSAS(呼吸暂停低通气指数≥30次/小时)的男性患者中采集外周血。采用定量聚合酶链反应(qPCR)检测外周血单个核细胞(PBMCs)中与中枢昼夜节律起搏器相关的基因(包括 、 、 )以及三个 基因( )的mRNA水平。
我们发现OSAS患者PBMCs中 (P值 = 0.022)的表达存在统计学显著差异,CPAP治疗未能使其恢复正常。我们还发现OSAS患者的慢波睡眠(SWS)含量大幅降低(P值 < 0.001),与快速眼动睡眠(REM)不同,CPAP治疗未能纠正这一现象(P值 = 0.875)。
CPAP治疗无法纠正OSAS患者核心生物钟基因表达的显著变化。由于CPAP治疗也无法使这些患者的SWS恢复正常,可能需要额外的治疗干预措施来增加SWS含量并补充CPAP的益处,以更有效地降低与OSAS患者相关的已知心血管风险增加。