Effects of <italic style="font-style: italic">Yuanzhi Powder</italic> （远志散） on Learning and Memory and Expression of Tight Junction Proteins in Hippocampus of Alzheimer's Disease Model Mice

Bin LI; Jiaxin LI; Yanwei HAO; Peijun XIE; Daoyin GONG; Yi ZHANG

doi:10.13288/j.11-2166/r.2022.06.012

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Effects of Yuanzhi Powder （远志散） on Learning and Memory and Expression of Tight Junction Proteins in Hippocampus of Alzheimer's Disease Model Mice

更新时间：2022-04-12

- Effects of Yuanzhi Powder （远志散） on Learning and Memory and Expression of Tight Junction Proteins in Hippocampus of Alzheimer's Disease Model Mice
- Journal of Traditional Chinese Medicine Vol. 63, Issue 6, Pages: 557-563(2022)
- 作者机构：
  
  成都中医药大学附属医院，四川省成都市十二桥路39号，610072
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2022.06.012
  CLC：
- Received：07 August 2021，
  
  Revised：2021-12-26，
  
  Published：17 March 2022
- 稿件说明：
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李斌,李佳欣,郝彦伟等.远志散对阿尔茨海默病模型小鼠学习记忆能力及海马紧密连接蛋白表达的影响[J].中医杂志,2022,63(06):557-563.

LI Bin,LI Jiaxin,HAO Yanwei,et al.Effects of Yuanzhi Powder （远志散） on Learning and Memory and Expression of Tight Junction Proteins in Hippocampus of Alzheimer's Disease Model Mice[J].Journal of Traditional Chinese Medicine,2022,63(06):557-563.
李斌,李佳欣,郝彦伟等.远志散对阿尔茨海默病模型小鼠学习记忆能力及海马紧密连接蛋白表达的影响[J].中医杂志,2022,63(06):557-563. DOI： 10.13288/j.11-2166/r.2022.06.012.

LI Bin,LI Jiaxin,HAO Yanwei,et al.Effects of Yuanzhi Powder （远志散） on Learning and Memory and Expression of Tight Junction Proteins in Hippocampus of Alzheimer's Disease Model Mice[J].Journal of Traditional Chinese Medicine,2022,63(06):557-563. DOI： 10.13288/j.11-2166/r.2022.06.012.

摘要

目的

探讨远志散治疗阿尔茨海默病的可能作用机制。

方法

30只快速老化（SAMP8）小鼠随机分为模型组、盐酸多奈哌齐组、远志散组，每组10只，另设10只抗快速老化小鼠（SAMR1小鼠）作为空白组。盐酸多奈哌齐组给予2 mg/（kg·d）盐酸多奈哌齐灌胃，远志散组给予12 g/（kg·d）远志散灌胃，灌胃量均为10 ml/kg；空白组、模型组以无菌水10 ml/kg灌胃。各组均每日1次，连续8周。采用Morris水迷宫实验观察各组小鼠学习记忆能力，HE染色检测海马CA1区神经元病理，免疫组化检测海马CA1区β淀粉样蛋白

1-42

（Aβ

1-42

）表达，硫磺素S（Thioflavine-S）染色观察海马β淀粉样蛋白（Aβ）聚集情况，Western blot法检测海马组织中胞质附着蛋白（ZO-1）、闭锁蛋白5、咬合蛋白表达。

结果

与空白组比较，模型组小鼠Morris水迷宫实验中第2、3、4天逃避潜伏期显著延长，进入有效区次数和有效区内停留时间显著减少（

＜0.05或

＜0.01）；病理结果显示小鼠神经细胞层数减少，固化萎缩的神经元数量明显增加；Aβ

1-42

蛋白在海马CA1区有丰富表达，Thioflavine-S荧光强度明显增强；海马ZO-1、闭锁蛋白5、咬合蛋白表达水平均明显下降（

＜0.01）。Morris水迷宫实验中盐酸多奈哌齐组与远志散组小鼠逃避潜伏期均逐日缩短（

＜0.05或

＜0.01），且第3、4天的逃避潜伏期显著短于同日的模型组，进入有效区次数和有效区停留时间均较模型组增加（

＜0.05或

＜0.01）；盐酸多奈哌齐组与远志散组小鼠神经元数量均较模型组增加，固化萎缩的神经元数量均减少；Thioflavine-S荧光强度均较模型组明显减弱，Aβ

1-42

蛋白在海马CA1区中均呈低表达；海马中ZO-1、闭锁蛋白5、咬合蛋白表达水平均高于模型组（

＜0.01）。远志散组与盐酸多奈哌齐组小鼠各指标比较差异均无统计学意义（

＞0.05）。

结论

远志散能提高SAMP8小鼠学习记忆能力，抑制Aβ在海马中异常聚集，其机制可能与提高海马紧密连接蛋白ZO-1、闭锁蛋白5、咬合蛋白表达和改善血脑屏障功能有关。

Abstract

Objective

To explore the possible mechanism of

Yuanzhi Powder

（远志散） in the treatment of Alzheimer's disease （AD）.

Methods

Thirty rapidly aging mice SAMP8 were randomly divided into a model group， donepezil hydrochloride group and

Yuanzhi Powder

group， with 10 rats in each group. Another 10 anti-rapidly aging mice SAMR1 were set as blank group. Donepezil hydrochloride at a concentration of 2 mg/（kg·d） and

Yuanzhi Powder

at a concentration of 12 g/（kg·d） were given by gavage to the corresponding group respectively， while sterile water was administered by gavage in the blank group and the model group. The dose was 10 ml/kg in all groups， and the interventions were administered once daily for 8 weeks. Morris water maze （MWM） was used to test the learning and memory. HE staining was used to detect neuronal pathology in hippocampal CA1 region. The expression of amyloid-β

1-42

（Aβ

1-42

） in hippocampal CA1 region was detected by immunohistochemistrym， while amyloid-β （Aβ） aggregation was observed through thioflavine-S staining. Western blotting was used to detect the expression of cytoplasmic attachment protein （ZO-1）， claudin-5 and occludin in hippocampus.

Results

Compared to those in the blank group， the escape latency on day 2， 3， 4 in the model group was prolonged significantly， and the number of entries into the target quadrant and the time spent in target quadrant using MWM were significantly reduced （

＜0.05 or

＜0.01）. The pathological results showed the layers of nerve cells decreased and the solidified atrophy neurons increased in the model group. Moreover， Aβ

1-42

proteins were abundantly expressed in hippocampal CA1 region， the fluorescence intensity of Thioflavine-S was significantly enhanced， and the expression levels of ZO-1， claudin-5 and occludin in the hippocampus were significantly decreased in the model group （

＜0.01）. The escape latency detected by WMW decreased day by day in the donepezil hydrochloride group and the

Yuanzhi Powder

group

，

and was significantly shorter than that in the model group on the same day， while on day 3 and day 4， the the number of entries into the target quadrant and the time spent in target quadrant increased （

＜0.05 or

＜0.01）. Compared to those in the model group， the layers of nerve cells significantly increased， while the solidified atrophy neurons decreased in donepezil hydrochloride group and the

Yuanzhi Powder

group. Moreover， the fluorescence intensity of Thioflavine-S was significantly weakened； Aβ

1-42

proteins was lowly expressed in the hippocampal CA1 region； and the expression levels of ZO-1， claudin-5 and occludin in the hippocampus were higher （

＜0.01）. There was no significant differences between

Yuanzhi Powder

group and donepezil hydrochloride group in all outcomes （

＞0.05）.

Conclusion

Yuanzhi Powder

can improve the learning and memory and inhibit the abnormal aggregation of Aβ in the hippocampus of SAMP8 mice. The mechanism may be related to its functions of increasing hippocampal tight junction protein ZO-1， oclaudin-5， and occludin expression and improving blood-brain barrier function.

关键词

Keywords

references

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Effects of Yuanzhi Powder （远志散） on Learning and Memory and Expression of Tight Junction Proteins in Hippocampus of Alzheimer's Disease Model Mice

DOI：10.13288/j.11-2166/r.2022.06.012

摘要

Abstract

关键词

Keywords

references