Shengyutang Improves Learning and Memory Ability of Sleep Deprived Mice by Regulating Levels of Monoamine Neurotransmitters in Hippocampus

Dan-dan WEI; Yu-jie LI; Yong-jie WANG; Shan-shan LI; Ming-hao ZHANG; Shi-qing JIANG

doi:10.13422/j.cnki.syfjx.20210402

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Shengyutang Improves Learning and Memory Ability of Sleep Deprived Mice by Regulating Levels of Monoamine Neurotransmitters in Hippocampus

Classic Prescriptions | 更新时间：2021-03-29

- Shengyutang Improves Learning and Memory Ability of Sleep Deprived Mice by Regulating Levels of Monoamine Neurotransmitters in Hippocampus
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 7, Pages: 1-8(2021)
- 作者机构：
  
  1.河南中医药大学，郑州 450046
  2.河南省第三人民医院，郑州 450000
  3.河南中医药大学第一附属医院，郑州 450000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20210402
  CLC： R2-0;R22;R285.5;R289
- Received：04 November 2020，
  
  Published Online：03 February 2021，
  
  Published：05 April 2021
- 稿件说明：
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魏丹丹,李玉洁,王永杰等.圣愈汤通过调节海马区单胺类神经递质水平改善睡眠剥夺小鼠学习、记忆能力[J].中国实验方剂学杂志,2021,27(07):1-8.

WEI Dan-dan,LI Yu-jie,WANG Yong-jie,et al.Shengyutang Improves Learning and Memory Ability of Sleep Deprived Mice by Regulating Levels of Monoamine Neurotransmitters in Hippocampus[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(07):1-8.
魏丹丹,李玉洁,王永杰等.圣愈汤通过调节海马区单胺类神经递质水平改善睡眠剥夺小鼠学习、记忆能力[J].中国实验方剂学杂志,2021,27(07):1-8. DOI： 10.13422/j.cnki.syfjx.20210402.

WEI Dan-dan,LI Yu-jie,WANG Yong-jie,et al.Shengyutang Improves Learning and Memory Ability of Sleep Deprived Mice by Regulating Levels of Monoamine Neurotransmitters in Hippocampus[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(07):1-8. DOI： 10.13422/j.cnki.syfjx.20210402.

摘要

目的

通过研究圣愈汤对海马区单胺类神经递质水平的影响，探讨圣愈汤改善睡眠剥夺（SD）小鼠学习、记忆能力的可能机制。

方法

建立SD小鼠模型，将50只成功造模的小鼠随机分为正常组，模型组，艾司唑仑组，圣愈汤低、高剂量组，每组10只。圣愈汤低、高剂量组分别以12.5，25 g·kg

-1

灌胃，模型组小鼠每日给予等剂量的生理盐水灌胃，连续灌胃8周。采用Morris水迷宫实验观察各组SD小鼠逃避潜伏期时间、穿越平台次数、目标象限停留时间等行为学变化情况；苏木素-伊红（HE）染色观察各组SD小鼠海马组织的病理形态学改变情况；高效液相色谱法检测5-羟色胺（5-HT），多巴胺（DA），肾上腺素（EP），去甲肾上腺素（NE），5-羟吲哚乙酸（5-HIAA），高香草酸（HVA），左旋多巴（

-DOPA）和3，4二羟基苯乙酸（DOPAC）等8种单胺类神经递质指标的表达水平；免疫组化法检测海马组织中c-Fos蛋白的表达水平。

结果

与正常组比较，模型组SD小鼠一般状态较差，出现严重疲劳状态；与模型组比较，圣愈汤各剂量组SD小鼠进食、活动、睡眠、毛色、对外界刺激反应等均有所改善。与正常组比较，模型组SD小鼠体质量明显降低（

0.05）；与模型组比较，圣愈汤高剂量组升高最明显（

0.05）。与正常组比较，模型组SD小鼠海马组织中细胞排列紊乱，形态不完整，间隙增大，神经元细胞数量减少；与模型组比较，圣愈汤各剂量组SD小鼠海马组织中神经元细胞均增多。与正常组比较，模型组SD小鼠逃避潜伏期时间明显延长，穿越平台次数、目标象限停留时间均显著降低（

0.01）；与模型组比较，圣愈汤各剂量组小鼠穿越平台次数、目标象限停留时间均明显增加（

0.05，

0.01）。与正常组比较，模型组小鼠5-HT，5-HIAA，

-DOPA，DOPAC，EP，NE，HVA，DA水平均明显降低（

0.05，

0.01）；与模型组比较，圣愈汤各剂量组5-HT，5-HIAA，

-DOPA，DOPAC，EP，NE，HVA，DA水平均明显提高（

0.05）。与正常组比较，模型组海马组织的c-Fos蛋白平均MD值显著升高（

0.01）；与模型组比较，圣愈汤各剂量组海马组织中c-Fos蛋白表达显著降低（

0.01）。

结论

圣愈汤能改善SD大鼠的学习、记忆能力，其作用机制可能与降低单胺类神经递质和c-Fos蛋白表达相关。

Abstract

Objective

To observe the effect of Shengyutang on the levels of monoamine neurotransmitters in the hippocampus， and explore its possible mechanism on improving the learning and memory abilities of sleep deprivation （SD） mice.

Method

The 50 mice were divided into normal group， model group， estazolam group， Shengyutang low and high dose groups， with 10 mice in each group. A multi-platform water environment was used to prepare SD mouse models. The low and high-dose Shengyutang groups received intragastric administration of 12.5， 25 g·kg

-1

， respectively. The mice in the model group were intragastrically administered with the same dose of normal saline daily for 8 weeks. Morris water maze experiment was used to observe the behavioral changes of SD mice in the evasion latency period， the number of crossing platforms， and the stay time in the target quadrant of each group. HE staining was used to observe the pathomorphological changes of the hippocampal tissue of each group. The expression levels of eight monoamine neurotransmitters including serotonin （5-HT），dopandne （DA），epinephrine （EP），norepinephrine （NE），5-hydroxyindole acetic acid（5-HIAA）， high vanillic acid （HVA）， levodopa（

-DOPA），and 3，4-dihydroxyphenylacetic acid（DOPAC）were detected by high performance liquid chromatography， and the expression levels of c-Fos protein in hippocampus were detected by immunohistochemistry.

Result

Compared with the normal group， the SD mice in the model group were in a poorer general state and severe fatigue was observed. Compared with the model group， SD mice in each dose group of Shengyutang got improved in eating， activity， sleep， hair color， and response to external stimuli. Compared with the normal group， the body weight of SD mice in the model group was significantly reduced （

0.05）， but the body weight in the Shengyutang high-dose group increased the most as compared with the model group （

0.05）. Compared with the normal group， the hippocampal cells in the model group were disorderly arranged， incomplete in shape， increased in gap and decreased in number. Compared with the model group， the number of neurons in the hippocampus of SD mice in each dose group of Shengyutang increased. Compared with the normal group， the escape latency time of SD mice in the model group was significantly prolonged， the times of crossing platform and the residence time in the target quadrant significantly decreased （

0.01）. Compared with the model group， the times of crossing platform and the residence time in the target quadrant of mice in each dose group of Shengyutang significantly increased （

0.05，

0.01）. Compared with the normal group， the levels of 5-HT， 5-HIAA，

-DOPA， DOPAC， EP， NE， HVA and DA in the model group significantly decreased （

0.05，

0.01）； but these levels in each dose group of Shengyutang were higher than those in model group （

0.05）. Compared with the normal group， the average MD value of c-Fos protein in the hippocampus of the model group significantly increased （

0.01）， and the expression levels of c-Fos protein in the hippocampus of Shengyutang groups were significantly lower than those in model group （

0.01）.

Conclusion

Shengyutang can improve the learning and memory abilities of SD rats， and its mechanism may be related to the decrease of monoamine neurotransmitter and c-Fos protein expression.

关键词

Keywords

references

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