Biomarkers for circadian rhythm disruption independent of time of day.

Biomarkers for circadian rhythm disruption independent of time of day.
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DOI:
10.1371/journal.pone.0127075
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Rodenburg W
Rodenburg W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Van Dycke KC;Pennings JL;van Oostrom CT;van Kerkhof LW;van Steeg H;van der Horst GT;Rodenburg W

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频繁的轮班工作会扰乱昼夜节律,长期下去可能会增加健康风险。目前评估昼夜节律紊乱(CRD)存在的生物标志物,包括褪黑激素、皮质醇和体温,需要24小时(“全天候”)测量,这是繁琐的。因此,这些标记物不适合用于大规模(人类)研究。本研究的目的是使用转录组学方法鉴定CRD的通用生物标志物,其独立于一天中的时间。雌性FVB小鼠在顺时针(CW)和逆时针(CCW)CRD方案中暴露于6个班次,并分别在基线和1个班次、6个班次、5天恢复期和14天恢复期后处死。在一天中的六个时间点,收集肝脏用于mRNA微阵列分析。使用分类方法,我们鉴定了一组生物标志物,其能够基于肝脏基因表达将样品分类为CRD或非破坏的。此外,我们确定差异表达的基因14天后,最后一个班次相比,基线的两个CRD协议。非昼夜节律基因差异表达的CW和CCW协议被认为是有用的,通用的标记CRD。在CRD动物与对照动物的血清样品中评价了一种候选标志物,即CD36。这些生物标志物可能有助于测量CRD,并可用于监测旨在预防或尽量减少慢性不良健康影响的干预策略的有效性。
Frequent shift work causes disruption of the circadian rhythm and might on the long-term result in increased health risk. Current biomarkers evaluating the presence of circadian rhythm disturbance (CRD), including melatonin, cortisol and body temperature, require 24-hr (“around the clock”) measurements, which is tedious. Therefore, these markers are not eligible to be used in large-scale (human) studies. The aim of the present study was to identify universal biomarkers for CRD independent of time of day using a transcriptomics approach. Female FVB mice were exposed to six shifts in a clockwise (CW) and counterclockwise (CCW) CRD protocol and sacrificed at baseline and after 1 shift, 6 shifts, 5 days recovery and 14 days recovery, respectively. At six time-points during the day, livers were collected for mRNA microarray analysis. Using a classification approach, we identified a set of biomarkers able to classify samples into either CRD or non-disrupted based on the hepatic gene expression. Furthermore, we identified differentially expressed genes 14 days after the last shift compared to baseline for both CRD protocols. Non-circadian genes differentially expressed upon both CW and CCW protocol were considered useful, universal markers for CRD. One candidate marker i.e. CD36 was evaluated in serum samples of the CRD animals versus controls. These biomarkers might be useful to measure CRD and can be used later on for monitoring the effectiveness of intervention strategies aiming to prevent or minimize chronic adverse health effects.
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