Effect of TSG on GSK3<italic style="font-style: italic">β</italic>，PKA and PP2A of APP/PS1/Tau Triple-transgenic Mice Dementia Model

Yan-zhao SU; Wen-xue WU; Chao-yu LIU; Wan-ying MENG; Zhen-zhong LI; Jian HUANG; Xiao-ying ZHU; Yan-hua LIAO; Zhong-shi HUANG

doi:10.13422/j.cnki.syfjx.20202305

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Effect of TSG on GSK3β，PKA and PP2A of APP/PS1/Tau Triple-transgenic Mice Dementia Model

更新时间：2021-12-03

- Effect of TSG on GSK3β，PKA and PP2A of APP/PS1/Tau Triple-transgenic Mice Dementia Model
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 4, Pages: 64-69(2021)
- 作者机构：
  
  1.广西中医药大学药学院，南宁 530200
  2.右江民族医学院基础医学院，广西百色 533000
  3.右江民族医学院药学院，广西百色 533000
  4.右江民族医学院临床医学院，广西百色 533000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20202305
  CLC： R2-0;R22;R285.5
- Received：03 September 2020，
  
  Published Online：04 November 2020，
  
  Published：20 February 2021
- 稿件说明：
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苏彦兆,吴文雪,刘超宇等.二苯乙烯苷对APP/PS1/Tau三转基因小鼠痴呆模型GSK3β，PKA，PP2A的影响[J].中国实验方剂学杂志,2021,27(04):64-69.

SU Yan-zhao,WU Wen-xue,LIU Chao-yu,et al.Effect of TSG on GSK3β，PKA and PP2A of APP/PS1/Tau Triple-transgenic Mice Dementia Model[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(04):64-69.
苏彦兆,吴文雪,刘超宇等.二苯乙烯苷对APP/PS1/Tau三转基因小鼠痴呆模型GSK3β，PKA，PP2A的影响[J].中国实验方剂学杂志,2021,27(04):64-69. DOI： 10.13422/j.cnki.syfjx.20202305.

SU Yan-zhao,WU Wen-xue,LIU Chao-yu,et al.Effect of TSG on GSK3β，PKA and PP2A of APP/PS1/Tau Triple-transgenic Mice Dementia Model[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(04):64-69. DOI： 10.13422/j.cnki.syfjx.20202305.

摘要

目的

观察二苯乙烯苷（TSG）对淀粉样前体蛋白/早老蛋白-1/Tau（APP/PS1/Tau）三转基因小鼠阿尔茨海默病（AD）模型脑组织中糖原合成酶激酶3

（GSK3

），环磷酸腺苷依赖的蛋白激酶（PKA），磷酸丝氨酰/磷酸苏氨酰蛋白磷酸酶2A（PP2A）的表达影响。

方法

8月龄APP/PS1/Tau三转基因小鼠45只，随机分为模型组、石杉碱甲组（石杉碱甲，0.15 mg·kg

-1

），TSG低、中、高剂量组（TSG，0.033，0.1，0.3 g·kg

-1

），每组9只。另取同龄C5B7L/6J小鼠9只为正常组。各组灌胃60 d相应药物后，采用苏木素-伊红（HE）染色观察小鼠海马神经元的一般结构；免疫组化（IHC）检测各组小鼠脑组织PKA蛋白的表达；实时荧光定量聚合酶链式反应（Real-time PCR）检测GSK3

，PKA，PP2A mRNA表达情况；蛋白免疫印迹法（Western blot）检测GSK3

，PP2A蛋白表达情况。

结果

与正常组比较，模型组小鼠神经元细胞的凋亡水平显著升高，GSK3

，PKA蛋白及mRNA表达水平显著升高（

0.01），PP2A蛋白及mRNA表达水平显著下调（

0.01）；与模型组比较，各给药组小鼠神经元细胞凋亡水平显著下调，GSK3

，PKA蛋白及mRNA表达水平明显下调（

0.05，

0.01），PP2A蛋白及mRNA表达水平明显升高（

0.05，

0.01）。

结论

TSG治疗AD的机制可能与降低GSK3

和PKA mRNA表达水平与蛋白表达水平，提高PP2A的mRNA表达水平与蛋白表达水平等机制有关。

Abstract

Objective

To observe the effect of tetrahydroxy stilbene glycoside （TSG） on the expression of glycogen synthase kinase 3

（GSK3

）， cyclic adenosine monophosphate-dependent protein kinase （PKA） and Serine/threonine phosphatase 2A（PP2A） in the brain of amyloid precursor protein/presenilin-1/Tau （APP/PS1/Tau） triple-transgenic mice dementia model.

Method

A total of forty-five 8-month-old APP/PS1/Tau transgenic mice were randomly divided into model group， positive control group （Huperzine-A， 0.15 mg·kg

-1

）， low， medium and high dose TSG groups （TSG， 0.033，0.1，0.3 g·kg

-1

）， with 9 mice in each group， and another nine C5B7L/6J mice of the same age were selected as normal control group. After 60 days of intragastric administration， the general structure of hippocampal neurons was observed by hematoxylin-eosin （HE） staining， immunohistochemical （IHC） was used to detect the expression of PKA protein in the brain of mice in each group， the mRNA expression levels of GSK3

， PKA and PP2A were detected by real time quantitative reverse transcription polymerase chain reaction （Real-time PCR）， and protein expression levels of GSK3

and PP2A were detected by Western blot.

Result

Compared with the normal control group， the apoptosis level of neurons in the model group was significantly increased， the protein and mRNA expression levels of GSK3

and PKA were significantly increased （

0.05，

0.01）， and the protein and mRNA expression levels of PP2A were significantly decreased （

0.05，

0.01）. Compared with the model group， the apoptosis level of neurons in each treatment group was significantly down-regulated， the protein and mRNA expression levels of GSK3

and PKA were significantly down-regulated （

0.05，

0.01）， and the protein and mRNA expression levels of PP2A were significantly increased （

0.05，

0.01）.

Conclusion

The mechanism of TSG in the treatment of Alzheimer's disease （AD） may be related to lowering the transcription and expression of GSK3

and PKA， increasing the transcription and expression of PP2A.

关键词

Keywords

references

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Effect of TSG on GSK3β，PKA and PP2A of APP/PS1/Tau Triple-transgenic Mice Dementia Model

DOI：10.13422/j.cnki.syfjx.20202305

摘要

Abstract

关键词

Keywords

references