天麻粉预防痴呆小鼠模型发病及其对抗氧化作用的影响

高玉梅; 王晓玲; 邓于新; 任家谋; 沈祥春; 官志忠; 齐晓岚

doi:10.13422/j.cnki.syfjx.20200337

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天麻粉预防痴呆小鼠模型发病及其对抗氧化作用的影响

药理 | 更新时间：2021-04-16

- 天麻粉预防痴呆小鼠模型发病及其对抗氧化作用的影响
- Effect of Gastrodiae Rhizoma Powder on Prevention of Dementia and Oxidation Resistance in Mice
- 中国实验方剂学杂志 2020年26卷第2期页码：52-58
- 作者机构：
  
  贵州医科大学　地方病与少数民族疾病教育部重点实验室，贵州省医学分子生物学重点实验室，药学院，贵阳　 550004
- 作者简介：
  
  [第一作者]　高玉梅，在读硕士，从事阿尔茨海默病研究，E-mail：1627986831@qq.com
  *齐晓岚，博士，教授，博士生导师，从事阿尔茨海默病研究，E-mail：xiaolan76@163.com
- 基金信息：
  
  国家自然科学基金项目(81860207);贵州省科技计划项目(黔科合基础（2019）1437号);2018年贵州省研究生教育创新计划项目(黔教合YJSCXJH（2018）041);教育部“长江学者和创新团队发展计划资助”项目(LRT13058)
- DOI：10.13422/j.cnki.syfjx.20200337
  中图分类号： R22; R24; R289; R285.5
- 收稿日期：2019-06-27，
  
  网络出版日期：2019-10-18，
  
  纸质出版日期：2020-01-20
- 稿件说明：
移动端阅览
高玉梅, 王晓玲, 邓于新, 等. 天麻粉预防痴呆小鼠模型发病及其对抗氧化作用的影响[J]. 中国实验方剂学杂志, 2020,26(2):52-58.

Yu-mei GAO, Xiao-ling WANG, Yu-xin DENG, et al. Effect of Gastrodiae Rhizoma Powder on Prevention of Dementia and Oxidation Resistance in Mice[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(2): 52-58.
高玉梅, 王晓玲, 邓于新, 等. 天麻粉预防痴呆小鼠模型发病及其对抗氧化作用的影响[J]. 中国实验方剂学杂志, 2020,26(2):52-58. DOI： 10.13422/j.cnki.syfjx.20200337.

Yu-mei GAO, Xiao-ling WANG, Yu-xin DENG, et al. Effect of Gastrodiae Rhizoma Powder on Prevention of Dementia and Oxidation Resistance in Mice[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(2): 52-58. DOI： 10.13422/j.cnki.syfjx.20200337.

摘要

目的：

研究长期灌胃天麻粉是否可以改善APP/PS1双转基因阿尔茨海默病(AD)模型小鼠学习记忆能力以及延缓AD进程，这些作用是否与调控Kelch样环氧氯丙胺相关蛋白1(Keap1)-核转录因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)抗氧化应激通路有关，进一步探讨天麻粉的神经保护作用机制以及对AD预防和治疗的作用。

方法：

APP/PS1双转基因小鼠模型，将实验小鼠分为5组，正常组，正常给药组，模型组，天麻粉预防组，天麻粉治疗组。正常给药组，天麻粉预防组在小鼠8周龄时每日灌胃同等剂量的天麻粉(1.5 g·kg

-1

)；正常组、模型组同时期给予等量的生理盐水，直至24周龄时行Morris水迷宫检测小鼠学习和记忆能力，天麻粉治疗组待小鼠22周龄时，连续2周每天灌胃同等剂量天麻粉(1.5 g·kg

-1

)，灌胃至24周龄时行Morris水迷宫检测小鼠穿越平台次数、逃避潜伏期及平台停留时间；提取小鼠海马组织RNA，实时荧光定量PCR(Real-time PCR)检测Nrf2，HO-1，Keap1的mRNA水平；蛋白免疫印迹法(Western blot)检测小鼠海马组织中Nrf2，HO-1，Keap1蛋白的表达水平。

结果：

与正常组比较，水迷宫检测结果显示，模型组小鼠的学习记忆能力显著降低(

0.01)；与模型组比较，天麻粉预防组、天麻粉治疗组小鼠学习记忆能力显著提高(

0.01)；与正常组比较，模型组小鼠海马组织中Nrf2，HO-1的mRNA及蛋白水平均有不同程度的降低(

0.05，

0.01)，与模型组比较，天麻粉预防组小鼠海马组织中Nrf2，HO-1的mRNA及蛋白水平均有不同程度的增高(

0.05，

0.01)，天麻粉治疗组Nrf2，HO-1 mRNA水平显著增高(

0.01)，Nrf2，HO-1蛋白表达水平变化差异无统计学意义，各组间Keap1的mRNA及蛋白水平变化无统计学差异。

结论：

Morris水迷宫及其他结果显示天麻粉能够改善APP/PS1小鼠的学习和记忆能力，且其可能通过调控Keap1-Nrf2/HO-1通路，增强下游抗氧化基因的表达发挥抗氧化功能，进而改善APP/PS1小鼠的学习记忆能力。

Abstract

Objective:

To study whether long-term administration of Gastrodiae Rhizoma powder can improve the learning and memory ability of APPswe/PSldE9 double transgenic (APP/PS1) Alzheimer' s disease(AD) model mice and delay the progress of AD whether these effects are related to the regulation of antioxidant stress pathway in Kelch-like epoxylopropylamine-related protein 1(Keap1)-nuclear factor E2 related factor 2 (Nrf2)/heme oxygenase(HO)-1

and further explore the neuroprotective mechanism of Gastrodiae Rhizoma powder and its role in the prevention and treatment of AD.

Method:

APP/PS1 double transgenic mice model

the mice consisted of five groups: normal

normal administration group

model group

Gastrodiae Rhizoma powder prevention group

Gastrodiae Rhizoma powder treatment group.The mice in the normal administration group and the Gastrodiae Rhizoma powder prevention group were given the same dose of Gastrodiae Rhizoma powder (1.5 g·kg

-1

) daily at the age of 8 weeks.The normal group and model group were given the same amount of normal saline at the same time

until 24 weeks old

Morris water maze was used to test the learning and memory ability of mice

and the treatment group was treated with Gastrodiae Rhizoma powder at 22 weeks old.The mice were given the same dose of Gastrodiae Rhizoma powder (1.5 g·kg

-1

) every day for 2 weeks.The number of crossing platform

escape latency and platform residence time of mice were detected by Morris water maze from 24 weeks old to 24 weeks old.RNA

Real-time PCR was extracted from mouse hippocampus to detect the mRNA level of Nrf2

HO-1

Keap1

and Western blot was used to detect the expression of Nrf2

HO-1

Keap1 protein in mouse hippocampus.

Result:

Compared with normal group

the water maze test showed that the learning and memory ability of model group was lower than that of the model group (

0.01)

and the learning and memory ability of Gastrodiae Rhizoma powder prevention group and Gastrodiae Rhizoma powder treatment group was significantly higher than that of model group (

0.01). Compared with normal group

the levels of Nrf2

HO-1 and protein in the hippocampus in model group decreased in varying degrees (

0.05). Compared with model group

Gastrodiae Rhizoma powder prevented Nrf2

in the hippocampus of mice in model group.The level of HO-1 in mRNA and protein increased in different degrees (

0.05

0.01). Levels of Nrf2

HO-1 mRNA in Gastrodiae Rhizoma powder treatment group was significantly higher than that in Gastrodiae Rhizoma powder group (

0.05). There was no significant difference in the expression of Nrf2

HO-1 protein.There was no significant difference in mRNA and protein levels of Keap1 among different groups.

Conclusion:

Morris water maze test and other results showed that Gastrodiae Rhizoma powder could improve the learning and memory ability of APP/PS1 mice

and it may enhance the expression of downstream antioxidant genes by regulating Keap1-Nrf2/HO-1 pathway.And then improve the learning and memory ability of APP/PS1 mice.

关键词

Keywords

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