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昼夜节律紊乱导致皮质醇节律、血液生化指标和血清 miRNA 谱发生变化。

Circadian misalignment leads to changes in cortisol rhythms, blood biochemical variables and serum miRNA profiles.

机构信息

State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

Sun Yat-sen University Instrumental Analysis & Research Center, Sun Yat-sen University, Guangzhou, 510275, China.

出版信息

Biochem Biophys Res Commun. 2021 Aug 27;567:9-16. doi: 10.1016/j.bbrc.2021.06.015. Epub 2021 Jun 12.

Abstract

The circadian clock plays a critical role in synchronizing the inner molecular, metabolic and physiological processes to environmental cues that cycle with a period of 24 h. Non-24 h and shift schedules are commonly used in maritime operations, and both of which can disturb circadian rhythms. In this study, we first conducted an experiment in which the volunteers followed a 3-d rotary schedule with consecutive shift in sleep time (rotatory schedule), and analyzed the changes in salivary cortisol rhythms and blood variables. Next we conducted another experiment in which the volunteers followed an 8 h-on and 4-h off schedule (non-24-h schedule) to compare the changes in blood/serum variables. The rotatory schedule led to elevated levels of serum cortisol during the early stage, and the phase became delayed during the early and late stages. Interestingly, both of the schedules caused comprehensive changes in blood/serum biochemical variables and increased phosphate levels. Furthermore, transcriptomic analysis of the plasma miRNAs from the volunteers following the rotatory schedule identified a subset of serum miRNAs targeting genes involved in circadian rhythms, sleep homeostasis, phosphate transport and multiple important physiological processes. Overexpression of miRNAs targeting the phosphate transport associated genes, SLC20A1 and SLC20A2, showed altered expression due to rotary schedule resulted in attenuated cellular levels of phosphate, which might account for the changed levels in serum phosphate. These findings would further our understanding of the deleterious effects of shift schedules and help to optimize and enhance the performances and welfare of personnel working on similar schedules.

摘要

生物钟在将内部分子、代谢和生理过程与以 24 小时为周期循环的环境线索同步方面起着关键作用。非 24 小时和轮班时间表在航海作业中经常使用,这两种情况都会打乱生物钟节律。在这项研究中,我们首先进行了一项实验,志愿者遵循连续改变睡眠时间的 3 天旋转时间表(旋转时间表),并分析唾液皮质醇节律和血液变量的变化。接下来,我们进行了另一个实验,志愿者遵循 8 小时工作和 4 小时休息时间表(非 24 小时时间表)以比较血液/血清变量的变化。旋转时间表导致血清皮质醇水平在早期升高,相位在早期和晚期延迟。有趣的是,这两种时间表都会导致血液/血清生化变量的全面变化,并增加磷酸盐水平。此外,对遵循旋转时间表的志愿者的血浆 miRNA 的转录组分析确定了一组针对涉及生物钟、睡眠稳态、磷酸盐转运和多个重要生理过程的基因的血清 miRNA。针对磷酸盐转运相关基因 SLC20A1 和 SLC20A2 的 miRNA 的过表达显示,由于旋转时间表导致的表达改变导致细胞内磷酸盐水平降低,这可能是血清磷酸盐水平变化的原因。这些发现将进一步加深我们对轮班时间表的有害影响的理解,并有助于优化和增强类似时间表上工作的人员的绩效和福利。

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