镇心省睡益智方及其精油对AD模型小鼠学习记忆的影响

罗俊; 张科楠; 肖帅; 汤丹丰; 吴玲; 郭园园; 郑琴

doi:10.13422/j.cnki.syfjx.20190938

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镇心省睡益智方及其精油对AD模型小鼠学习记忆的影响

药理 | 更新时间：2021-02-09

- 镇心省睡益智方及其精油对AD模型小鼠学习记忆的影响
- Effect of Zhenxin Xingshui Yizhi Fang and Its Essential Oil Extract on Ability of Learning and Memory in Alzheimer's Disease Model Mice
- 中国实验方剂学杂志 2019年25卷第9期页码：74-81
- 作者机构：
  
  江西中医药大学，南昌　 330004
- 作者简介：
  
  罗俊，在读硕士，从事中药新剂型和新技术研究，E-mail：douya677358@163.com
  郑琴，博士，教授，博士生导师，从事中药新剂型和新技术研究，E-mail：zhengqin912006@163.com
- 基金信息：
  
  江西省科技创新人才重点项目（“5511”工程专项）(20171BCB18001)
- DOI：10.13422/j.cnki.syfjx.20190938
  中图分类号： R289; R338.2+ 4; R743; R745.1
- 收稿日期：2018-12-08，
  
  网络出版日期：2019-01-23，
  
  纸质出版日期：2019-05-05
- 稿件说明：
移动端阅览
罗俊, 张科楠, 肖帅, 等. 镇心省睡益智方及其精油对AD模型小鼠学习记忆的影响[J]. 中国实验方剂学杂志, 2019,25(9):74-81.

jun LUO, Ke-nan ZHANG, Shuai XIAO, et al. Effect of Zhenxin Xingshui Yizhi Fang and Its Essential Oil Extract on Ability of Learning and Memory in Alzheimer's Disease Model Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 74-81.
罗俊, 张科楠, 肖帅, 等. 镇心省睡益智方及其精油对AD模型小鼠学习记忆的影响[J]. 中国实验方剂学杂志, 2019,25(9):74-81. DOI： 10.13422/j.cnki.syfjx.20190938.

jun LUO, Ke-nan ZHANG, Shuai XIAO, et al. Effect of Zhenxin Xingshui Yizhi Fang and Its Essential Oil Extract on Ability of Learning and Memory in Alzheimer's Disease Model Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 74-81. DOI： 10.13422/j.cnki.syfjx.20190938.

摘要

目的：

观察镇心省睡益智方水提液及其精油对

淀粉样前体蛋白基因／早老素基因(APP/PS1)双转基因小鼠学习记忆的影响并探讨其可能机制。

方法：

采用APP/PS1双转基因痴呆小鼠及同月龄相同遗传背景C57BL/6JNju小鼠2种小鼠。C57BL/6JNju小鼠作为正常组，APP/PS1双转基因痴呆小鼠随机分为模型组，镇心省睡益智方精油低、高质量浓度组(12.13，48.50 mg·L

－1

)，镇心省睡益智方水提液组(0.46 g·kg

－1

)，每组12只。每天给药1次，连续给药22 d。给药结束后采用跳台实验、Morris水迷宫实验对小鼠行为学能力进行检测，采用尼氏染色观察海马CA1区神经元变化，采用硫磺素(ThS)染色观察海马DG区老年斑(SP)沉积，采用免疫组化法检测小鼠脑组织中葡萄糖转运蛋白1(GLUT1)，胰岛素受体底物-1(IRS-1)的表达，采用酶联免疫吸附测定(ELISA)检测小鼠海马组织中乙酰胆碱(ACH)，

-氨基丁酸(GABA)，谷氨酸(GLU)含量的变化。

结果：

与正常组比较，模型组小鼠跳台实验潜伏期显著缩短，错误次数显著增加(

0.01)，Morris水迷宫实验定位航行逃避潜伏期明显延长(

0.05，

0.01)，海马CA1区神经元出现缺失，DG区出现明显的老年斑沉积(

0.05)，ACH

GLUT1含量均显著下降(

0.01)，GABA

GLU水平及IRS-1的表达均显著升高(

0.01)；与模型组比较，各给药组均可显著延长小鼠跳台实验潜伏期、减少跳台错误次数(

0.01)，明显降低定位航行小鼠逃避潜伏期(

0.05，

0.01)，可一定程度保护小鼠海马CA1区神经元，减少DG区老年斑沉积(

0.05，

0.01)，明显增加小鼠脑组织中ACH

GLUT1表达(

0.05，

0.01)，显著降低GABA

GLU水平及IRS-1的表达(

0.01)。

结论：

镇心省睡益智方水提液及其精油能够改善APP/PS1小鼠的学习记忆行为，保护神经元，增加脑组织GLUT1的表达，减少脑组织IRS-1的表达，减少老年斑沉积，升高ACH含量，降低GABA

GLU含量，可能是其防治阿尔茨海默症的机制。

Abstract

Objective:

The present study was designed to investigate the modulating effect of Zhenxin Xingshui Yizhi Fang and its essential oil extract on cognitive deficits in mice.

Method:

For the purpose of this study 5 months old APP/PS1 double transgenic mice and wild-type C57BL/6JNju were selected as experimental animals. Then APP/PS1 double transgenic mice were randomly divided into model group

essential oil low and high-dose groups (12.13

48.50 mg·L

-1

)

Zhenxin Xingshui Yizhi Fang group (0.46 g·kg

-1

). Meanwhile

wild-type C57BL/6JNju mice were used as a normal group. APP/PS1 double transgenic mice were treated with Zhenxin Xingshui Yizhi Fang and its essential oil extract for 22 consecutive days.Mice were subjected to a Morris water maze test and a platform test in order to determine their cognitive effect. Nissl's staining was used to observe pathological changes in brain tissue. Meanwhile

senile plaques (SP) were observed by employing Thioflavin-S staining. The expression of glucose transporter 1 (GLUT1) and insulin receptor substrate-1 (IRS-1) were analyzed using immunohistochemistry techniques. The levels of neurotransmitters such as acetylcholine (ACH)

glutamate (GLU) and

-aminobutyric acid (GABA) in the hippocampus were quantified by enzyme-linked immunosorbent assay(ELISA).

Result:

The memory function was significantly reduced in model group

and severe brain injury and neuronal apoptosis were also observed in comparison to normal group (

0.05

0.01). Compared with the model group

Zhenxin Xingshui Yizhi Fang and its essential oil extract improved previous learning and memory impairments (

0.05

0.01)

and the levels of SP

IRS-1

GLU

GABA (except essential oil low dose group) were significantly reduced (

0.01)

meanwhile the levels of ACH and GLUT1 were significantly improved (

0.05

0.01).

Conclusion:

These results indicate that Zhenxin Xingshui Yizhi Fang and its essential oil extract could ameliorate cognitive deficits and GLUT1 and IRS-1 could be a possible therapeutic target for AD. It may be an interesting approach to the treatment of Alzheimer's disease.

关键词

Keywords

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