Effect of Anmeidan in Improving Learning and Memory Levels of Sleep Deprived Rats Through Mitochondrial Mediated Hippocampal Neuronal Apoptosis

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

doi:10.13422/j.cnki.syfjx.20202280

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Effect of Anmeidan in Improving Learning and Memory Levels of Sleep Deprived Rats Through Mitochondrial Mediated Hippocampal Neuronal Apoptosis

Classic Prescriptions | 更新时间：2020-12-10

- Effect of Anmeidan in Improving Learning and Memory Levels of Sleep Deprived Rats Through Mitochondrial Mediated Hippocampal Neuronal Apoptosis
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 24, Pages: 38-44(2020)
- 作者机构：
  
  湖北中医药大学基础医学院，武汉 430065
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20202280
  CLC： R2-0;R22;R285.5;R289
- Received：07 April 2020，
  
  Published Online：24 July 2020，
  
  Published：20 December 2020
- 稿件说明：
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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.

XIE Guang-jing,XU Bo,HUANG Pan-pan,et al.Effect of Anmeidan in Improving Learning and Memory Levels of Sleep Deprived Rats Through Mitochondrial Mediated Hippocampal Neuronal Apoptosis[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(24):38-44.
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. DOI： 10.13422/j.cnki.syfjx.20202280.

XIE Guang-jing,XU Bo,HUANG Pan-pan,et al.Effect of Anmeidan in Improving Learning and Memory Levels of Sleep Deprived Rats Through Mitochondrial Mediated Hippocampal Neuronal Apoptosis[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(24):38-44. DOI： 10.13422/j.cnki.syfjx.20202280.

摘要

目的

探讨安寐丹通过线粒体介导海马神经细胞凋亡对睡眠剥夺大鼠学习记忆的影响。

方法

48只SD大鼠随机分为正常组、模型组、安寐丹低、中、高剂量（4.86，9.72，19.44 g·kg

-1

·d

-1

）组和艾司唑仑组（0.1 mg·kg

-1

·d

-1

），每组8只。通过自制睡眠剥夺箱进行持续性睡眠剥夺14 d。以Morris水迷宫检测大鼠的学习记忆水平，酶联免疫吸附测定（ELISA）检测海马组织B淋巴细胞瘤-2（Bcl-2），Bcl-2相关X蛋白（Bax）的含量。透射电镜观察海马区神经元线粒体形态结构，免疫荧光和实时荧光定量聚合酶链式反应（Real-time PCR）分别检测海马区细胞色素C（Cyt-C），半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）蛋白及Bcl-2，Bax mRNA表达。

结果

与正常组比较，模型组上平台潜伏期、游泳总路程延长，初次到达平台时间延长，跨越平台次数减少，目标象限时间显著降低（

0.01），Bcl-2蛋白及mRNA水平下降，Bax蛋白及mRNA水平显著升高（

0.01），线粒体结构破坏，嵴断裂，肿胀变形；Cyt-C，Caspase-3蛋白及mRNA表达显著升高（

0.01）；与模型组比较，安寐丹低、中、高剂量组明显改善SD大鼠空间探索和定位航行水平（

0.05，

0.01），Bcl-2蛋白及mRNA水平升高，Bax蛋白及mRNA水平明显降低（

0.05，

0.01）；线粒体损伤改善，水肿减轻；Cyt-C，Caspase-3蛋白及mRNA表达显著下降（

0.01）。

结论

安寐丹能够改善睡眠剥夺大鼠学习记忆水平，其作用与线粒体介导的海马神经细胞凋亡，降低Cyt-C，Caspase-3等蛋白表达相关。

Abstract

Objective

To explore the effect of Anmeidan （AMD） on the learning and memory levels of sleep deprived rats through mitochondrial mediated hippocampal neuronal apoptosis pathway.

Method

Forty-eight SD rats were randomly divided into blank group， model group， low， medium， high-dose AMD groups （4.86， 9.72， 19.44 g·kg

-1

·d

-1

） and estazolam group （0.1 mg·kg

-1

·d

-1

）. Insomnia model was prepared by self-made sleep deprivation box for 14 days. Morris water maze was used to detect learning and memory levels， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of cytochrome C （Cyt-C）， cysteine aspartic acid protease-3 （Caspase-3） in hippocampus. Transmission electron microscopy （TEM） was used to observe the morphological structure of mitochondria in hippocampus. Protein and mRNA expressions of Cyt-C， Caspase-3， Bcl-2， Bax were detected by immunofluorescence （IF） and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） respectively.

Result

In the model group， the incubation period of the platform and the total distance of swimming and the time of first arriving platform were prolonged， the number of platform crossing and the time of target quadrant movement were reduced， protein and mRNA expressions of Bcl-2 dropped， protein and mRNA expressions of Bax increased （

0.01）， and mitochondrial structure was abnormal with crista fracture， swelling and deformation. And protein and mRNA expressions of Cyt-C， Caspase-3 increased significantly （

0.01）. Low， medium and high-dose AMD groups could improve levels of space exploration and navigation of SD rats （

0.01）， increase protein and mRNA expressions of Bcl-2， decrease protein and mRNA expressions of Bax， improve the damage of mitochondria， and decrease the protein and mRNA expressions of Cyt-C， Caspase-3 （

0.01）.

Conclusion

AMD can improve the learning and memory levels of SD rats， the effect is related to the mitochondrial mediated hippocampal neuronal apoptosis pathway and decrease of Cyt-C and Caspase-3 expressions.

关键词

Keywords

references

BUYSSE D J ， ANCOLI-ISRAEL S ， EDINGER J D ， et al . Recommendations for a standard research assessment of insomnia ［J］. Sleep ， 2006 ， 29 （ 9 ）： 1155 - 1173 .

中国睡眠研究会 . 中国失眠症诊断和治疗指南［J］. 中华医学杂志， 2017 ， 97 （ 24 ）： 1844 - 1856 .

LISMAN J ， COOPER K ， SEHGAL M ， et al . Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability ［J］. Nat Neurosci ， 2018 ， 21 （ 3 ）： 309 - 314 .

吴惠涓，赵忠新，黄流清 . 睡眠对记忆巩固及突触可塑性影响的临床与实验研究进展［J］. 中华神经医学杂志， 2009 ， 8 （ 4 ）： 419 - 422 .

FORTIER-BROCHU E ， MORIN C M . Cognitive impairment in individuals with insomnia：clinical significance and correlates ［J］. Sleep ， 2014 ， 37 （ 11 ）： 1787 - 1798 .

WILCKENS K A ， HALL M H ， NEBES R D ， et al . Changes in cognitive performance are associated with changes in sleep in older adults with insomnia ［J］. Behav Sleep Med ， 2016 ， 14 （ 3 ）： 295 - 310 .

FORTIER-BROCHU É ， MORIN C M . Cognitive impairment in individuals with insomnia： clinical significance and correlates ［J］. Sleep ， 2014 ， 37 （ 11 ）： 1787 - 1798 .

OSORIO R S ， PIRRAGLIA E ， LUIS F ， et al . Greater risk of Alzheimer's disease in older adults with insomnia ［J］. J Am Geriatr Soc ， 2011 ， 59 （ 3 ）： 559 - 562 .

MALLE C ， EUSTACHE F ， RAUCHS G . The role of sleep in memory consolidation： effects of age and Alzheimer's disease ［J］. Biol Aujourdhui ， 2015 ， 209 （ 3 ）： 261 - 272 .

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 .

FERREIRA L B ， OLIVEIRA S L ， RAYA J ， et al . Bombesin administration impairs memory and does not reverse memory deficit caused by sleep deprivation ［J］. Behav Brain Res ， 2017 ， 331 ： 20 - 24 .

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

IDAN E ， DAVID Z ， ADI T ， et al . Sleep-dependent structural synaptic plasticity of inhibitory synapses in the dendrites of hypocretin/orexin neurons ［J］. Mol Neurobiol ， 2016 ， 54 （ 8 ）： 6581 - 6597 .

SAYGIN M ， OZGUNER M F ， ONDER O ， et al . The impact of sleep deprivation on hippocampal-mediated learning and memory in rats ［J］. Bratisl Lek Listy ， 2017 ， 118 （ 7 ）： 408 - 416 .

CAO Y ， LI Q ， LIU L ， et al . Modafinil protects hippocampal neurons by suppressing excessive autophagy and apoptosis in mice with sleep deprivation ［J］. Br J Pharmacol ， 2019 ， 176 （ 9 ）： 1282 - 1297 .

SINGH N . Apoptosis in health and disease and modulation of apoptosis for therapy： an overview ［J］. Indian J Clin Biochem ， 2007 ， 22 （ 2 ）： 6 - 16 .

AHMAD RATHER M ， JUSTIN THENMOZHI A ， MANIVASAGAM T ， et al . Neuroprotective role of asiatic acid in aluminium chloride induced rat model of Alzheimer's disease ［J］. Front Biosci ， 2018 ， 10 （ 1 ）： 262 - 275 .

SALIMIAN N ， PEYMANI M ， GHAEDI K ， et al . Modulation in miR-200a/SIRT1axis is associated with apoptosis in MPP+-induced SH-SY5Y cells ［J］. Gene ， 2018 ， 674 （ 20 ）： 25 - 30 .

JIANG W B ， CHEN Y Y ， LI B ， et al . DBA-induced caspase-3-dependent apoptosis occurs through mitochondrial translocation of cyt-c in rat hippocampus ［J］. Mol Biosyst ， 2017 ， 13 （ 9 ）： 1863 - 1873 .

MAURYA S R ， MAHALAKSHMI R . Mitochondrial VDAC2 and cell homeostasis：highlighting hidden structural features and unique functionalities ［J］. Biol Rev Camb Philos Soc ， 2017 ， 92 （ 4 ）： 1843 - 1858 .

LUO J ， YU L ， XIE G ， et al . Study on the mitochondrial apoptosis pathways of small cell lung cancer H446 cells induced by Trichinella spiralis muscle larvae ESPs ［J］. Parasitology ， 2017 ， 144 （ 6 ）： 1 - 8 .

JIANG W ， CHEN Y ， LI B ， et al . DBA-induced caspase-3-dependent apoptosis occurs through mitochondrial translocation of cyt-c in rat hippocampus ［J］. Mol Bio Syst ， 2017 ， 13 （ 9 ）： 1863 - 1873 .

WANG Q E ， HAN C ， ZHANG B ， et al . Nucleotide excision repair factor XPC enhances DNA damage-induced apoptosis by downregulating the antiapoptotic short isoform of Caspase-2 ［J］. Cancer Res ， 72 （ 3 ）： 666 - 675 .

CHOU W H ， LIU K L ， SHIH Y L ， et al . Ouabain induces apoptotic cell death through Caspase- and mitochondria-dependent pathways in human osteosarcoma U-2 OS cells ［J］. Anticancer Res ， 2018 ， 38 （ 1 ）： 169 - 178 .

LIU Z ， ZHAO X ， LIU B ， et al . Jujuboside A，a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by A β 1-42 ［J］. Eur J Pharmacol ， 2014 ， 738 （ 1 ）： 206 - 213 .

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