Department of Neurology, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung City 807, Taiwan.
Life Sci. 2012 Aug 21;91(3-4):127-31. doi: 10.1016/j.lfs.2012.06.024. Epub 2012 Jul 4.
Our study investigated the role of circadian rhythm in the pathogenesis of sleep disturbance in patients with chronic kidney disease (CKD) based on an animal model.
Sixteen Sprague-Dawley (SD) rats (eight from 5/6 nephrectomized CKD group and eight from control group) were used for electroencephalography (EEG) and electromyography (EMG) recording. Eight rats (four from CKD and four from control group) were sacrificed at six Zeitgeber time (ZT) points and determined the mRNA expression of clock genes, rPer1, rPer2 and rBMAL1b in the hypothalamus.
Our results demonstrated that both slow wave sleep (SWS) and rapid eye movement (REM) sleep were significantly increased in the ZT22-24 Zeitgeber time point of the dark period in the CKD rats when compared with those sleep architectures obtained from the control rats. The CKD-induced sleep disruptions were associated with significant upregulations of rPer1 (in ZT2, ZT6 and ZT14) and rPer2 mRNA expression (in ZT2 and ZT14) in the hypothalamus.
Our study elucidated that the increases of SWS and REM sleep during ZT22-24 of the dark period in the CKD rats might be due to the enhancement of rPer1 and rPer2 clock genes in the hypothalamus, suggesting that disrupted circadian rhythm plays a role in the pathogenesis of sleep disturbance in patients with CKD.
本研究通过动物模型探讨了昼夜节律在慢性肾脏病（CKD）患者睡眠障碍发病机制中的作用。
使用 16 只 Sprague-Dawley（SD）大鼠（5/6 肾切除 CKD 组 8 只，对照组 8 只）进行脑电图（EEG）和肌电图（EMG）记录。8 只大鼠（CKD 组 4 只，对照组 4 只）在 6 个 Zeitgeber 时间点（ZT）处死，并测定下丘脑时钟基因 rPer1、rPer2 和 rBMAL1b 的 mRNA 表达。
结果表明，与对照组相比，CKD 大鼠在暗期的 ZT22-24 Zeitgeber 时间点，慢波睡眠（SWS）和快速眼动（REM）睡眠均显著增加。CKD 引起的睡眠障碍与下丘脑 rPer1（ZT2、ZT6 和 ZT14）和 rPer2 mRNA 表达（ZT2 和 ZT14）的显著上调有关。
本研究表明，CKD 大鼠在暗期的 ZT22-24 期间 SWS 和 REM 睡眠增加，可能是由于下丘脑 rPer1 和 rPer2 时钟基因的增强，提示昼夜节律紊乱在 CKD 患者睡眠障碍的发病机制中起作用。
