BMAL1 Disrupted Intrinsic Diurnal Oscillation in Rat Cerebrovascular Contractility of Simulated Microgravity Rats by Altering Circadian Regulation of miR-103/CaV1.2 Signal Pathway
BMAL1 Disrupted Intrinsic Diurnal Oscillation in Rat Cerebrovascular Contractility of Simulated Microgravity Rats by Altering Circadian Regulation of miR-103/CaV1.2 Signal Pathway
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BMAL1 通过改变 miR-103/CaV1.2 信号通路的昼夜节律调节来破坏模拟微重力大鼠脑血管收缩力的内在昼夜振荡
DOI：
10.3390/ijms20163947
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发表时间：
2019-08-02
影响因子：
5.6
通讯作者：
Xie, Man-Jiang
中科院分区：
文献类型：
--
作者：
Chen, Li;Zhang, Bin;Xie, Man-Jiang
脑动脉功能和结构的适应性改变可能是航天后立位耐力不良发生的根本原因之一。此外，新兴的研究发现，许多心血管功能表现出昼夜节律。一些证据表明，太空飞行可能会通过扰乱昼夜节律来增加宇航员的心血管风险。然而，微重力是否干扰血管收缩力的昼夜变化以及微重力是否影响生物钟系统仍然是未知的。对Sprague-Dawley大鼠进行28天的后肢减重，以模拟微重力对血管系统的影响。通过研究血管收缩反应性和肌张力来估计脑血管收缩力。通过记录全细胞电流、评估蛋白和mRNA表达来确定CaV1.2通道的昼夜调节。筛选出与Ca 2+信号相关的候选miRNA。最后，确定了脑血管收缩性昼夜节律调节的潜在途径。本研究的主要结果如下：（1）生物钟基因BMAL 1可诱导miR-103的表达，进而在转录后水平调节大鼠脑动脉CaV 1. 2通道的昼夜节律;（2）模拟微重力通过改变BMAL 1/miR-103/CaV 1. 2信号通路的昼夜节律调节，破坏大鼠脑血管收缩力的固有昼夜振荡。
The functional and structural adaptations in cerebral arteries could be one of the fundamental causes in the occurrence of orthostatic intolerance after space flight. In addition, emerging studies have found that many cardiovascular functions exhibit circadian rhythm. Several lines of evidence suggest that space flight might increase an astronaut’s cardiovascular risks by disrupting circadian rhythm. However, it remains unknown whether microgravity disrupts the diurnal variation in vascular contractility and whether microgravity impacts on circadian clock system. Sprague-Dawley rats were subjected to 28-day hindlimb-unweighting to simulate the effects of microgravity on vasculature. Cerebrovascular contractility was estimated by investigating vasoconstrictor responsiveness and myogenic tone. The circadian regulation of CaV1.2 channel was determined by recording whole-cell currents, evaluating protein and mRNA expressions. Then the candidate miRNA in relation with Ca2+ signal was screened. Lastly, the underlying pathway involved in circadian regulation of cerebrovascular contractility was determined. The major findings of this study are: (1) The clock gene BMAL1 could induce the expression of miR-103, and in turn modulate the circadian regulation of CaV1.2 channel in rat cerebral arteries at post-transcriptional level; and (2) simulated microgravity disrupted intrinsic diurnal oscillation in rat cerebrovascular contractility by altering circadian regulation of BMAL1/miR-103/CaV1.2 signal pathway.