Effect of Hei Xiaoyaosan on Expressions of Aβ<sub>1-42</sub>, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice

Hong-yan WU; Chun-lin MA; Shu-mei CUI; Kai-min ZHU; Jia-nan LIU; Qing-tao Zeng

doi:10.13422/j.cnki.syfjx.20190502

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Effect of Hei Xiaoyaosan on Expressions of Aβ_1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice

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- Effect of Hei Xiaoyaosan on Expressions of Aβ_1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 5, Pages: 36-42(2019)
- 作者机构：
  
  1.深圳市罗湖区人民医院，广东　深圳　 518020；
  2.深圳市罗湖区中医院，广东　深圳　 518001；
  3.甘肃中医药大学，兰州　 730000；
  4.定西市第二人民医院，甘肃　定西　 743000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190502
  CLC： R2-0;R22;R285.5;R289
- Received：22 August 2018，
  
  Published Online：27 November 2018，
  
  Published：05 March 2019
- 稿件说明：
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Hong-yan WU, Chun-lin MA, Shu-mei CUI, et al. Effect of Hei Xiaoyaosan on Expressions of Aβ_1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 36-42.
DOI：

Hong-yan WU, Chun-lin MA, Shu-mei CUI, et al. Effect of Hei Xiaoyaosan on Expressions of Aβ_1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 36-42. DOI： 10.13422/j.cnki.syfjx.20190502.

摘要

目的：

研究黑逍遥散对阿尔茨海默症(Alzheimer disease

AD)小鼠海马区

淀粉样多肽1-42(

-amyloid 1-42 peptide

1-42

)，糖原合成酶激酶-3(glycogen synthase kinase-3

GSK-3

)，脑啡肽酶(neprilysin

NEP)，胰岛素抵抗酶(insulin-degrading enzyme

IDE)表达的影响。

方法：

42只APP/PSI双转基因小鼠称体质量后，按随机原则分为4组，分别为模型组，阳性药组（盐酸多奈哌齐，3.25mg·kg

－1

），黑逍遥散高、低剂量组(6

3g·kg

－1

)。10只同月龄、同种系的野生型C57BL/6J小鼠为正常组。连续灌胃12周后，Morris水迷宫予以行为学检测，苏木素-伊红(HE)染色观察海马神经元的形态改变，采用免疫组化技术分别检测小鼠海马区A

1-42

，GSK-3

，NEP

IDE蛋白的表达。

结果：

治疗3个月后，与正常组比较，AD模型组小鼠，逃避潜伏期均延长，跨原平台次数减少(

0.01)，小鼠海马区A

1-42

，GSK-3

蛋白阳性表达显著增强，NEP与IDE蛋白阳性表达显著减弱(

0.01)，HE染色显示AD模型小鼠海马神经细胞损伤严重；与模型组比较，用药各组小鼠的逃避潜伏期均显著缩短、跨原平台次数均显著增加(

0.05，

0.01)，小鼠海马区A

1-42

，GSK-3

蛋白阳性表达显著减弱，NEP与IDE蛋白阳性表达显著增强(

0.05，

0.01)，HE染色显示各治疗组小鼠海马神经细胞损伤减轻。

结论：

黑逍遥散能够显著改善AD小鼠的学习记忆能力，可能与调节A

在海马区的异常沉积和降解作用等方面来减轻AD小鼠认知能力损伤有关。

Abstract

Objective:

To observe the effect of Hei Xiaoyaosan on expressions of

-amyloid 1-42 peptide(A

1-42

)

glycogen synthase kinase-3

(GSK-3

)

neprilysin(NEP)

insulin-degrading enzyme(IDE) in the hippocampus area of Alzheimer's dementia mice.

Method:

After weighing

42 APP/PSI bivalent transgenic mice were randomly divided into 4 groups: 10 mice in the model group

10 mice in the positive drug control group

11 mice in the high-dose Hei Xiaoyaosan group

and 11 mice in the low-dose Hei Xiaoyaosan group; 10 wild C57BL/6J mice of the same age and strain were used for negative control group. Drugs were administered to mice by gavage once a day for 12 weeks. Then the behavior of all the mice were detected by Morris water maze

the morphological changes in hippocampal neurons were observed by hematoxylineosin(HE) staining

the expressions of A

1-42

GSK-3

NEP and IDE proteins in hippocampus were detected by immunohistochemistry.

Result:

After 3 months of treatment

compared with negative control groups

the average escaping latency periods prolonged significantly

and the number of cross-platform was decreased significantly in model group (

0.01)

the expressions of A

1-42

and GSK-3

proteins in model mice hippocampus were significantly increased (

0.01)

the expressions of NEP and IDE proteins in model mice hippocampus were significantly decreased (

0.01)

suggesting serious damage of hippocampal nerve cells in model group mice according to HE staining; compared with the model group

the escape latency of drug groups were significantly shortened

and the number of crossing platforms was significantly increased (

0.05)

the expressions of A

1-42

and GSK-3

proteins in the hippocampus of drug groups were significantly decreased (

0.01)

the expressions of NEP and IDE proteins in the hippocampus of drug groups were significantly increased (

0.05

0.01)

suggesting the alleviation in the damage of hippocampal nerve cells in drug groups.

Conclusion:

Hei Xiaoyaosan can significantly improve the learning and memory abilities of AD mice

which may be related to the reduction of cognitive impairment in AD mice by regulating abnormal deposition and degradating A

in the hippocampus.

关键词

Keywords

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⁰

Effect of Hei Xiaoyaosan on Expressions of Aβ1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice

DOI：10.13422/j.cnki.syfjx.20190502

摘要

Abstract

关键词

Keywords

references

Effect of Hei Xiaoyaosan on Expressions of Aβ_1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice