Influence of sleep apnea syndrome on clock gene dysfunction

阻塞性睡眠呼吸暂停综合征（OSAS）在临床上引起睡眠中的间歇性缺氧（IH）。在体外培养的人肺腺癌上皮细胞（A549）中，IH条件下炎症细胞因子白介素-6 (IL-6) mRNA水平显著升高，这是由于核因子- kb （NF-KB）的信号通路被激活，NF-KB是IL-6的有效转录激活因子。然而，IH处理细胞对时钟基因表达的影响很小。OSAS患者血清IL-6浓度明显高于健康者，但经CPAP治疗后，OSAS患者血清IL-6升高水平降至健康者水平。IH可以激活炎症反应的信号转导，但不能激活生物钟调节。血清IL-6升高可引起OSAS患者全身性炎症。

Obstructive sleep apnea syndrome (OSAS) clinically causes intermittent hypoxia (IH) during sleep. The levels of an inflammation cytokine interleukin-6 (IL-6) mRNA significantly elevated by IH condition in cultured human lung adenocarcinoma epithelial cells (A549), due to activation of the signaling pathway of nuclear factor-KB (NF-KB) which is a potent transcriptional activator of IL-6. However, the treatment of cells with IH had little effect on clock gene expressions. Serum concentrations of IL-6 in OSAS patients were significantly higher than in healthy subjects, but elevated levels of IL-6 in OSAS patients fell to the level of healthy subjects after CPAP therapy. The condition of IH can activate signal transduction to an inflammatory response, but not to circadian clock regulation. The increase of serum IL-6 may cause systemic inflammation in patients with OSAS.