Anmeidan Modulates Circadian Rhythm of Spontaneous Activity and Influences Clock Proteins in Sleep-deprived Rats

Guang-jing XIE; Bo XU; Pan-pan HUANG; Ping WANG

doi:10.13422/j.cnki.syfjx.20212309

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Anmeidan Modulates Circadian Rhythm of Spontaneous Activity and Influences Clock Proteins in Sleep-deprived Rats

更新时间：2022-03-07

- Anmeidan Modulates Circadian Rhythm of Spontaneous Activity and Influences Clock Proteins in Sleep-deprived Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 7, Pages: 33-39(2022)
- 作者机构：
  
  湖北中医药大学老年医学研究所，武汉 430065
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20212309
  CLC： R2-0;R22;R285.5;R289;R33
- Received：15 August 2021，
  
  Published Online：24 July 2020，
  
  Published：05 April 2022
- 稿件说明：
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谢光璟,徐波,黄攀攀等.安寐丹对睡眠剥夺大鼠自发活动昼夜节律的调节及对生物钟蛋白的影响[J].中国实验方剂学杂志,2022,28(07):33-39.

XIE Guang-jing,XU Bo,HUANG Pan-pan,et al.Anmeidan Modulates Circadian Rhythm of Spontaneous Activity and Influences Clock Proteins in Sleep-deprived Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(07):33-39.
谢光璟,徐波,黄攀攀等.安寐丹对睡眠剥夺大鼠自发活动昼夜节律的调节及对生物钟蛋白的影响[J].中国实验方剂学杂志,2022,28(07):33-39. DOI： 10.13422/j.cnki.syfjx.20212309.

XIE Guang-jing,XU Bo,HUANG Pan-pan,et al.Anmeidan Modulates Circadian Rhythm of Spontaneous Activity and Influences Clock Proteins in Sleep-deprived Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(07):33-39. DOI： 10.13422/j.cnki.syfjx.20212309.

摘要

目的

探讨安寐丹（AMD）对睡眠剥夺大鼠生物节律及相关蛋白表达的影响。

方法

80只大鼠随机分为空白组、模型组、安寐丹组和褪黑素组。自制睡眠剥夺箱进行睡眠剥夺4周，正常与模型组给予等容生理盐水，安寐丹组给药9.09 g·kg

-1

·d

-1

。褪黑素组给药0.27 g·kg

-1

·d

-1

。自发活动视频分析系统评价自发活动昼夜节律，苏木素-伊红（HE）染色观察下丘脑组织形态，尼氏染色观察下丘脑组织神经元及尼氏小体，蛋白免疫印迹法（Western blot）检测下丘脑cAMP反应元件结合蛋白（CREB）/近日钟基因（Per）通路蛋白表达，免疫组化检测生物钟蛋白核心时钟基因1（Bmal1）、时钟基因（Clock）、Per1、隐花色素1基因（Cry1）的表达。

结果

模型组昼夜节律相对紊乱，在6个节点活动时间较空白组显著增加，活动速度及活动次数增加（

0.01）；同时神经元数量减少，排列稀疏，胞核皱缩或碎裂；尼氏体数量减少，出现明显丢失，尼氏体着色变淡；p-CREB、Per1蛋白相对表达降低，Bmal1、Clock、Per1、Cry1蛋白阳性率下降（

0.01）。与模型组比较，安寐丹组大鼠活动时间、活动速度及活动次数均下降（

0.01）；神经元损伤减轻，数量增加，部分核仁清晰，胞浆明显，尼氏体数量增加；p-CREB、Per1蛋白相对表达升高，Bmal1、Clock、Per1、Cry1蛋白阳性率上升（

0.01）。

结论

安寐丹改善睡眠剥夺大鼠自发活动昼夜节律，其作用可能通过调节CREB/Per信号通路，增加生物钟蛋白Bmal1、Clock、Per1、Cry1表达有关。

Abstract

Objective

To investigate the effect of Anmeidan （AMD） on biological rhythm and related protein expression in sleep-deprived rats.

Method

A total of 80 SD rats were randomized into control group （Ctrl， equivalent volume of saline）， model group （SD， equivalent volume of saline）， AMD group （9.09 g·kg

-1

·d

-1

）， and melatonin group （MT， 0.27 g·kg

-1

·d

-1

）. Insomnia was induced in rats by self-made sleep deprivation box （4 weeks）. Circadian rhythm of spontaneous activity was evaluated by spontaneous activity video analysis system. Morphology of hypothalamus was observed based on hematoxylin-eosin （HE） staining， and the histomorphology of hypothalamus neurons and the Nissl's bodies based on Nissl staining. Western blotting was employed to detect the expression of hypothalamic proteins in cAMP-response element binding protein （CREB）/clock gene period （Per） pathway， and immunohistochemistry the expression of brain and muscle ARNT-like protein 1 （Bmal1）， Clock， Per1， and cryptochrome circadian regulator 1 （Cry1）.

Result

The model group demonstrated circadian rhythm disorder， as manifested by the significant increase in activity time in 6 designated time periods compared with the control group， and the rise in the activity speed and frequency （

0.01）. Moreover， model group showed decrease in number of neurons which were sparsely arranged with shrunken or fragmented nuclei， reduction in number and loss of Nissl's bodies with light color， and drop in the relative expression of p-CREB and Per1， and the positive rate of Bmal1， Clock， Per1， and Cry1 （

0.01）. Compared with model group， AMD group demonstrated reduction in time， speed， and frequency of activity （

0.01）. Moreover， the AMD group also showed alleviation of neuronal damage （

0.01）， and increase in the number of neurons with clear nuclei and cytoplasm in some， and the number of Nissl's bodies. AMD raised the expression of p-CREB and Per1 proteins， and the positive rate of Bmal1， Clock， Per1， and Cry1 （

0.01）.

Conclusion

AMD ameliorated spontaneous circadian rhythm of sleep-deprived rats by regulating CREB/Per signaling pathway and further increasing the expression of Bmal1， Clock， Per1， and Cry1.

关键词

Keywords

references

WHEATON A G ， LIU Y ， PERRY G S ， et al . Effect of short sleep duration on daily activities-United States，2005-2008 ［J］. MMWR Morb Mortal Wkly Rep ， 2011 ， 60 （ 8 ）： 239 - 242 .

ZHOU H R ， WU J R ， BEI L ， et al . Hydroalcoholic extract from Abelmoschus manihot （Linn.） Medicus flower reverses sleep deprivation-evoked learning and memory deficit ［J］. Food Funct ， 2020 ， 11 （ 10 ）： 8978 - 8986 .

ZHU B ， SHI C ， PARK C G ， et al . Effects of sleep restriction on metabolism-related parameters in healthy adults： a comprehensive review and meta-analysis of randomized controlled trials ［J］. Sleep Med Rev ， 2019 ， 45 ： 18 - 30 .

HOR C N ， YEUNG J ， JAN M ， et al . Sleep-wake-driven and circadian contributions to daily rhythms in gene expression and chromatin accessibility in the murine cortex ［J］. Proc Natl Acad Sci USA ， 2019 ， 116 （ 51 ）： 25773 - 25783 .

OROZCO-SOLIS R ， MONTELLIER E ， AGUILAR-ARNAL L ， et al . A circadian genomic signature common to ketamine and sleep deprivation in the anterior cingulate cortex ［J］. Biol Psychiatry ， 2017 ， 82 （ 5 ）： 351 - 360 .

LU Y ， LIU B ， MA J ， et al . Disruption of circadian transcriptome in lung by acute sleep deprivation ［J］. Front Genet ， 2021 ， 12 ： 664334 .

徐波 . 《内经》生命周期理论探讨及安寐丹对睡眠剥夺模型Orexin信号通路作用研究［D］. 武汉：湖北中医药大学， 2019 .

谢光璟，徐波，黄攀攀，等 . 安寐丹通过线粒体介导的海马神经细胞凋亡改善睡眠剥夺模型大鼠的学习记忆水平［J］. 中国实验方剂学杂志， 2020 ， 26 （ 24 ）： 38 - 44 .

MCDERMOTT C M ， LAHOSTE G J ， CHEN C ， et al . Sleep deprivation causes behavioral，synaptic，and membrane excitability alterations in hippocampal neurons ［J］. J Neurosci ， 2003 ， 23 （ 29 ）： 9687 - 9695 .

陈奇 . 中药药理研究方法学（精）［M］. 2版 .北京：人民卫生出版社， 2006 .

王静，侯婉婷，秦雪梅，等 . 昼夜节律的相关研究进展［J］. 中国中药杂志， 2021 ， 46 （ 13 ）： 3240 - 3248 .

DEURVEILHER S ， SEMBA K . Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat：implications for the circadian control of behavioural state ［J］. Neuroscience ， 2005 ， 130 （ 1 ）： 165 - 183 .

HASTINGS M H ， MAYWOOD E S ， BRANCACCIO M . Generation of circadian rhythms in the suprachiasmatic nucleus ［J］. Nat Rev Neurosci ， 2018 ， 19 （ 8 ）： 453 - 469 .

JHA P K ， H BOUÂOUDA H ， GOURMELEN S ， et al . Sleep deprivation and caffeine treatment potentiate photic resetting of the master circadian clock in a diurnal rodent ［J］. J Neurosci ， 2017 ， 37 （ 16 ）： 3241 - 3216 .

DEBOER T ， DÉTÁRI L ， MEIJER J H . Long term effects of sleep deprivation on the mammalian circadian pacemaker ［J］. Sleep ， 2007 ， 30 （ 3 ）： 257 - 262 .

LAVIV T ， SCHOLL B ， PARRA-BUENO P ， et al . In vivo imaging of the coupling between neuronal and CREB activity in the mouse brain ［J］. Neuron ， 2020 ， 105 （ 5 ）： 799 - 812 .

YOKOTA S ， YAMAMOTO M ， MORIYA T ， et al . Involvement of calcium-calmodulin protein kinase but not mitogen-activated protein kinase in light-induced phase delays and Per gene expression in the suprachiasmatic nucleus of the hamster ［J］. J Neurochem ， 2001 ， 77 （ 2 ）： 618 - 627 .

KOPP C ， ALBRECHT U ， ZHENG B ， et al . Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice ［J］. Eur J Neurosci ， 2002 ， 16 （ 6 ）： 1099 - 1106 .

WISOR J P ， O'HARA B F ， TERAO A ， et al . A role for cryptochromes in sleep regulation ［J］. BMC Neurosci ， 2002 ， 3 （ 1 ）： 20 .

BUNGER M K ， WILSBACHER L D ， MORAN S M ， et al . Mop3 is an essential component of the master circadian pacemaker in mammals ［J］. Cell ， 2000 ， 103 （ 7 ）： 1009 - 1017 .

NAYLOR E ， BERGMANN B M ， KRAUSKI K ， et al . The circadian clock mutation alters sleep homeostasis in the mouse ［J］. J Neurosci ， 2000 ， 20 （ 21 ）： 8138 - 8143 .

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