Clock Genes Disruption in the Intensive Care Unit
Clock Genes Disruption in the Intensive Care Unit
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DOI：
10.1177/0885066619876572
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发表时间：
2019-09-11
影响因子：
3.1
通讯作者：
Perez, Silvia
中科院分区：
文献类型：
--
作者：
Diaz, Elena;Diaz, Irene;Perez, Silvia
背景：重症监护病房（ICU）环境由于环境和其他非光同步因子而扰乱昼夜节律。这篇文章的主要目的是确定危重患者在ICU停留1周后是否在分子水平上发生了去硬化。研究方法：研究了神经ICU患者（n = 11）入院后第一天（1天）和1周后（1周）全天4个时间点（6、12、18和24小时）的Clock、Bmal 1、Cry 1和Per2基因的节律。从神经ICU患者获得人全血样品。分离总RNA，将每个样品逆转录为互补DNA，并进行定量聚合酶链反应（PCRq）。利用傅立叶级数研究了可能的节律。结果：1周后，时钟基因节律性完全消失。4个时钟基因的mRNA表达在ICU入院后第1天呈现节律性。Clock、Bmal 1和Per2 mRNA在1周后的表达在4个时间点的研究中相似，在分析的4个时间点之间没有显著波动。讨论：在ICU入院后的第一天，存在有节律的mRNA表达。然而，ICU停留1周会影响生物钟的分子机制，从而产生时间中断。昼夜节律紊乱与几种病理学的风险相关，因此，似乎很明显，ICU保持恒定条件可能会对患者的演变产生不利影响，并且恢复时钟基因表达的昼夜节律紊乱可能会导致患者更好的临床演变。结论：神经科ICU患者存在生物钟基因破坏。光疗法和褪黑素治疗可以减少ICU停留时间对生物钟的影响，从而促进患者的康复。
Background: Intensive care unit (ICU) environment disrupts the circadian rhythms due to environmental and other nonphotic synchronizers. The main purpose of this article is to establish whether critically patients have desynchronization at the molecular level after 1 week of stay in the ICU. Methods: The rhythm of Clock, Bmal1, Cry1, and Per2 genes in neuro-ICU patients (n = 11) on the first day after admission in the unit (1 day) and 1 week later (1 week) was studied, 4 time points throughout the day, at 6, 12, 18, and 24 hours. Human whole blood samples were obtained from neuro-ICU patients. The total RNA was isolated and each sample was reverse transcribed to complementary DNA and quantitative polymerase chain reaction (PCRq) was performed. The possible rhythm was studied using Fourier Series. Results: After 1 week, the clock gene rhythmicity completely disappeared. Messenger RNA (mRNA) expression for the 4 clock genes was shown rhythmicity at the first day after admission in the ICU. Circadian rhythmicity for none of them was observed but rather, ultradian rhythmicity was found. The expression of Clock, Bmal1, and Per2 mRNA after 1 week was similar in the 4-time point studies without significant fluctuation among the 4 time points analyzed. Discussion: Rhythmic mRNA expression is present at the first day after admission in the ICU. However, ICU stay during 1 week affects the molecular machinery of the biological clock generating chronodisruption. Circadian disruption is associated with the risk of several pathologies, thus, it seems to be clear that ICU stay in constant conditions could adversely affect patient evolution and probably, circadian resynchronization restoring clock gene expression could lead to a better clinical evolution of the patient. Conclusions: Clock genes disruption is observed in neuro-ICU patients. Light therapy as well as melatonin treatment could reduce the impact of ICU stay period in biological clock, thereby improving patients' recovery.