Effect of Zhenxin Xingshui Yizhi Fang and Its Essential Oil Extract on Ability of Learning and Memory in Alzheimer's Disease Model Mice

jun LUO; Ke-nan ZHANG; Shuai XIAO; Dan-feng TANG; Lin WU; Yuan-yuan GUO; Qin ZHENG

doi:10.13422/j.cnki.syfjx.20190938

您当前的位置：

首页 >

文章列表页 >

Effect of Zhenxin Xingshui Yizhi Fang and Its Essential Oil Extract on Ability of Learning and Memory in Alzheimer's Disease Model Mice

Pharmacology | 更新时间：2021-02-09

- Effect of Zhenxin Xingshui Yizhi Fang and Its Essential Oil Extract on Ability of Learning and Memory in Alzheimer's Disease Model Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 9, Pages: 74-81(2019)
- 作者机构：
  
  江西中医药大学，南昌　 330004
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190938
  CLC： R289; R338.2+ 4; R743; R745.1
- Received：08 December 2018，
  
  Published Online：23 January 2019，
  
  Published：05 May 2019
- 稿件说明：
移动端阅览
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：

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

references

PENG D , YUAN X , ZHU R . Memantine hydrochloride in the treatment of dementia subtypes [J]. J Clin Neurosci , 2013 , 20 ( 11 ): 1482 - 1485 .

张雅静，纪勇，石志鸿．阿尔茨海默病的药物治疗进展 [J]. 中国城乡企业卫生， 2016 , 31 ( 5 ): 15 - 18 .

毕祥云，陈学香．阿尔茨海默病相关治疗的研究进展 [J]. 中华保健医学杂志， 2017 , 19 ( 3 ): 275 - 277 .

Demetrius L A , Driver J . Alzheimer's as a metabolic disease [J]. Biogerontology , 2013 , 14 ( 6 ): 641 - 649 .

Monte S M D L , TONG M . Brain metabolic dysfunction at the core of Alzheimer's disease [J]. Biochem Pharmacol , 2014 , 88 ( 4 ): 548 - 559 .

Blonz E R . Alzheimer's disease as the product of a progressive energy deficiency syndrome in the central nervous system: the neuroenergetic hypothesis [J]. Alzheimers Dis , 2017 , 60 ( 4 ): 1223 - 1229 .

Duara R , Grady C , Haxby J , et al . Positron emission tomography in Alzheimer's disease [J]. Neurology , 1986 , 36 ( 7 ): 879 - 887 .

Denver P , English A , Mcclean P L . Inflammation, insulin signaling and cognitive function in aged APP/PS1 mice [J]. Brain Behav Immun , 2018 , doi: 10.1016/j.bbi.2018.03.032 http://doi.org/10.1016/j.bbi.2018.03.032 .

Choeiri C , Staines W , Messier C . Immunohistochemical localization and quantification of glucose transporters in the mouse brain [J]. Neurosci , 2002 , 111 ( 1 ): 19 - 34 .

[唐]孙思邈 . 千金翼方 [M]. 北京 : 人民卫生出版社 , 1983 : 188 .

范昌斌，杨旭东．镇心醒睡益智方治疗嗜睡症14例 [J]. 基层中药杂志， 2000 , 14 ( 3 ): 61 .

贺密会，刘明，周小江，等．镇心省睡益智方对快动眼睡眠剥夺大鼠促醒和认知功能的影响 [J]. 解放军药学学报， 2013 , 29 ( 5 ): 415 - 419 .

杭天依，李光武，徐金勇．嗅觉通路与大脑关联作用的研究进展 [J]. 立体定向和功能性神经外科杂志， 2013 , 26 ( 2 ): 125 - 128 .

谭洁，罗敏敏．嗅球对嗅觉信息的处理 [J]. 生物物理学报， 2010 , 26 ( 3 ): 194 - 208 .

Dobetsberger C , Buchbauer G . Actions of essential oils on the central nervous system: an updated review [J]. Flavour Fragr J , 2011 , 26 ( 5 ): 300 - 316 .

Moss L , Rouse M , Wesnes K A , et al . Differential effects of the aromas of salvia species on memory and mood [J]. Hum Psychopharmacol Clin Exp , 2010 , 25 ( 5 ): 388 - 396 .

Jimbo D , Kimura Y , Taniguchi M , et al . Effect of aromatherapy on patients with Alzheimer's disease [J]. Psychogeriatrics , 2010 , 9 ( 4 ): 173 - 179 .

胡泓博，夏传余，李光武．丁香酚吸嗅对MCAO模型大鼠脑源性神经营养因子的影响 [J]. 中风与神经疾病杂志， 2015 , 32 ( 1 ): 28 - 32 .

徐叔云，卞如濂，陈修．《药理实验方法学》第二版出版发行 [J]. 中国药理学通报， 1992 ( 1 ): 19 .

魏伟，吴希美，李元建．药理实验方法学 [M]．北京：人民卫生出版社， 2010 ： 19 .

闫盼盼，闫国立，詹向红，等． Morris水迷宫实验设计的统计学方法探析 [J]. 中华中医药学刊， 2013 , 31 ( 2 ): 264 - 266 .

Kalita J , Kumar V , Misra U K , et al . Memory and learning dysfunction following copper toxicity: biochemical and immunohistochemical basis [J]. Mol Neurobiol , 2017 , 55 ( 2 ): 1 - 12 .

Kim H Y , Kim H V , Jo S , et al . EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid- β oligomers and plaques [J]. Nat Commun , 2016 , 7 ( 8997 ): 10755 .

张玲 . HDAC6在APPswe/PS1dE9阿尔茨海默病转基因模型小鼠发病机制中的作用 [D]. 北京：北京协和医学院， 2014 .

郝徐艺，罗思，程淑意，等．当归芍药散对AD细胞模型铜离子介导的A β 聚集的影响 [J]. 中国实验方剂学杂志， 2019 , 25 ( 6 ): 45 - 51 .

Minkeviciene R , Ihalainen J , Malm T , et al . Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice [J]. J Neurochem , 2008 , 105 ( 3 ): 584 - 594 .

Hashimoto E , Ozawa H , Saito T , et al . Impairment of Gsαfunction in human brain cortex of Alzheimer's disease: comparison with normal aging [J]. J Neural Transm , 2004 , 111 ( 3 ): 311 - 322 .

Patching S G . Glucose transporters at the blood-brain barrier: function, regulation and gateways for drug delivery [J]. Mol Neurobiol , 2016 , 54 ( 2 ): 1046 - 1077 .

Szutowicz A , Bielarczyk H , Ronowska A , et al . Intracellular redistribution of acetyl-CoA, the pivotal point in differential susceptibility of cholinergic neurons and glial cells to neurodegenerative signals [J]. Biochem Soc T , 2014 , 42 ( 4 ): 1101 - 1106 .

PAN J , KAO Y L , Joshi S , et al . Activation of Rac1 by phosphatidylinositol 3-kinase in vivo : role in activation of mitogen-activated protein kinase (MAPK) pathways and retinoic acid-induced neuronal differentiation of SH-SY5Y cells [J]. J Neurochem , 2010 , 93 ( 3 ): 571 - 583 .

何瑛琨．基于脑能量代谢研究半夏泻心汤的神经保护作用 [D]．北京：北京中医药大学， 2016 .

卢成淑，冯宁，南国，等．石菖蒲及其活性成分防治阿尔茨海默病的研究进展 [J]. 中草药， 2016 , 47 ( 7 ): 1236 - 1242 .

GENG Y , LI C , LIU J , et al . Beta-asarone improves cognitive function by suppressing neuronal apoptosis in the beta-amyloid hippocampus injection rats [J]. Biol Pharm Bull , 2010 , 33 ( 5 ): 836 - 843 .

金虹，徐国波，黄毅．石菖蒲抑酶活性的实验研究 [J]. 时珍国医国药， 2009 , 20 ( 9 ): 2241 - 2242 .

吴宾，方永奇．石菖蒲益智作用的物质基础及其机理研究 [J]. 中医药学刊， 2004 , 22 ( 9 ): 1635 - 1636,1641 .

杨天鹏，唐敏，刘巧琼，等．丁香酚通过嗅觉通路改善昆明鼠学习记忆的机制 [J]. 中国康复医学杂志， 2007 , 22 ( 6 ): 487 - 489,508,477 .

张陶珍，荣巍巍，李清，等．远志的研究进展 [J]. 中草药， 2016 , 47 ( 13 ): 2381 - 2389 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰