Effect of Hei Xiaoyaosan on Expressions of APP, PERK in Hippocampus Area of Alzheimer's Dementia Mice

Shu-mei CUI; Hong-yan WU; Chun-lin MA; Qing-tao ZENG; Jia-nan LIU; Kai-min ZHU

doi:10.13422/j.cnki.syfjx.20192101

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Effect of Hei Xiaoyaosan on Expressions of APP, PERK in Hippocampus Area of Alzheimer's Dementia Mice

Pharmacology | 更新时间：2021-02-09

- Effect of Hei Xiaoyaosan on Expressions of APP, PERK in Hippocampus Area of Alzheimer's Dementia Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 22, Pages: 8-14(2019)
- 作者机构：
  
  1.甘肃中医药大学，兰州　 730000；
  2.深圳市罗湖区人民医院，广东　深圳　 518020；
  3.深圳市罗湖区中医院，广东　深圳　 518001；
  4.定西市第二人民医院，甘肃　定西　 743000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20192101
  CLC： R2-0; R22; R285.5; R289
- Received：29 March 2019，
  
  Published Online：18 July 2019，
  
  Published：20 November 2019
- 稿件说明：
移动端阅览
Shu-mei CUI, Hong-yan WU, Chun-lin MA, et al. Effect of Hei Xiaoyaosan on Expressions of APP, PERK in Hippocampus Area of Alzheimer's Dementia Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(22): 8-14.
DOI：

Shu-mei CUI, Hong-yan WU, Chun-lin MA, et al. Effect of Hei Xiaoyaosan on Expressions of APP, PERK in Hippocampus Area of Alzheimer's Dementia Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(22): 8-14. DOI： 10.13422/j.cnki.syfjx.20192101.

摘要

目的：

研究黑逍遥散对阿尔茨海默症(AD)模型小鼠海马神经元内质网应激的影响，包括行为学、组织病理学及淀粉样前体蛋白(APP)，类蛋白激酶内质网激酶(PERK)等因子的表达。

方法：

使用SPF级的4月龄双转基因(APP/PS1)雄性小鼠42只随机分为黑逍遥散高、低剂量组(6，3 g·kg

－1

)，盐酸多奈哌齐组(3.25 mg·kg

－1

)及模型组4组，同种系同月龄C57BL小鼠10只作为正常组。首先适应环境1周，经不同药物干预治疗2个月后，用Morris水迷宫行为学检测每组小鼠的学习和记忆能力；再治疗1个月后，通过光镜来观察每组小鼠海马区组织病理学改变；免疫组化、实时荧光定量聚合酶链式反应(Real-time PCR)检测小鼠海马区细胞内质网组织中APP，PERK蛋白及mRNA的表达情况。

结果：

药物干预治疗后，与正常组比较，模型组小鼠的逃避潜伏期显著延长(

0.01)；模型组小鼠海马区内神经元严重损伤；模型组APP，PERK的表达量显著升高(

0.01)。与模型组比较，各给药组小鼠逃逸潜伏期均明显缩短(

0.05，

0.01)；海马区内神经元损伤程度均减轻；APP，PERK的表达均明显降低(

0.05)。

结论：

黑逍遥散能够显著改善AD小鼠的学习记忆能力，可能与减少内质网过度应激反应等方面来减轻AD小鼠认知能力损伤有关。

Abstract

Objective:

To study the effect of Hei Xiaoyaosan on endoplasmic reticulum stress in hippocampal neurons of Alzheimer's disease (AD) model mice

including behavioral

histopathology and amyloid precursor protein (APP)

protein kinase endoplasmic reticulum kinase (PERK) expressions.

Method:

The 42 4-month-old SPF-grade double transgenic (APP/PS1) mice were randomly divided into the high-dose group and the low-dose group

the donepezil hydrochloride group and the model group

and 10 C57BL mice of the same age were used as the blank group. Firstly

they were adapted to the environment for one week. After 2 months of treatment with different drug interventions

Morris water maze behavior was used to test the learning and memory abilities of each group of mice. After 1 month of treatment

histopathological changes in the hippocampus of each group of mice were observed by light microscopy. The expressions of APP

PERK protein and mRNA in the endoplasmic reticulum of hippocampus were detected by immunohistochemistry (IHC) and real-time fluorescent quantitative polymerase chain reaction (Real-time PCR).

Result:

After drug intervention

compared with the blank group

the escape latency of the AD model group was significantly prolonged (

0.01)

the neurons in the hippocampus of the model group were severely damaged

and the expressions of APP and PERK in the model group were significantly increased (

0.01). In the comparison model group

the escape latency of the mice in each treatment group was significantly shortened (

0.05

0.01)

the degree of neuronal damage in the hippocampus of each treatment group was alleviated

and the positive expressions of APP and PERK in each treatment group were weakened (

0.05).

Conclusion:

Hei Xiaoyaosan can significantly improve the learning and memory abilities of AD mice

which may be related to the reduction of the excessive stress response of endoplasmic reticulum to alleviate cognitive impairment in AD mice.

关键词

Keywords

references

李娟，姚遥，韩怀钦，等．苦参碱对LPS诱导的阿尔茨海默病小鼠模型学习记忆功能和脑内神经炎症的影响 [J]．中国实验方剂学杂志， 2018 ， 24 ( 24 )： 134 - 139 ．

董贤慧，柴锡庆．阿尔茨海默病发病机制研究进展 [J]．中国老年学杂志， 2014 ， 34 ( 20 )： 5906 - 5912 ．

Listed N A . Dementia cases set to triple by 2050 but still largely ignored [J]. Media Centre , 2012 , 110 ( 8 ): 88 - 92 .

Zaghi J , Goldenson B , Inayathullah M , et al . Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy [J]. Acta Neuropathol , 2009 , 117 ( 2 ): 111 - 115 .

张志辰，温彬宇，高俊峰，等．地黄饮子调节PERK/elF2α通路抑制能量代谢障碍AD小鼠脑内β淀粉样蛋白累积的作用机制 [J]．中国实验方剂学杂志， 2018 ， 24 ( 21 )： 91 - 98 ．

袁旭，李政，王晓天，等．中药及其有效成分在抗癫痫中的作用与机制 [J]．中国中药杂志， 2019 ， 44 ( 1 )： 9 - 18 ．

Kumar D , Ganeshpurkar A , Kumar D , et al . Secretase inhibitors for the treatment of Alzheimer' s disease: long road ahead [J]. Eur J Med Chem , 2018 , 148 ( 22 ): 165 - 169 .

LIU Q , ZHAO D , JI Y X , et al . Lei T role of glucose-regulated protein 78 in early brain injury after experimental subarachnoid hemorrhage in rats [J]. Med Sci , 2016 , 36 ( 2 ): 168 - 173 .

Anderson A J , SU J H , Cotman C W . DNA damage and apoptosis in Alzheimer' s disease: coloca zation with C-jun immunoactivity. Relationship to brain area and effect of postmortem delay [J]. J Neurosci , 2011 , 16 ( 9 ): 1710 - 1719 .

许浩，胡祥友，秦松，等．阿尔茨海默病脑海马凋亡神经元发生率增高 [J]．中国神经科学杂志， 2002 ， 18 ( 1 )： 462 - 465 ．

王清任．《医林改错》白话解 [M]．人民军医出版社， 2007 ： 16 - 17 ．

刘佳楠．黑逍遥散对APP/PS1双转基因小鼠海马区内Aβ清除机制的研究 [D]．兰州：甘肃中医药大学， 2018 ．

李海龙，王虎平，刘建鸿，等．黑逍遥散对Aβ25-35诱导AD大鼠模型脑组织和血清SOD，GSH-Px及MDA的影响 [J]．中国实验方剂学杂志， 2013 ， 19 ( 21 )： 186 - 189 ．

吴红彦，马春林，崔淑梅，等．黑逍遥散对AD模型小鼠海马Aβ-(1-42)，GSK-3β，NEP，IDE表达的影响 [J]．中国实验方剂学杂志， 2019 ， 25 ( 5 )： 36 - 42 ．

曹文渊． p18在APP运输和加工过程中的功能研究 [D]．北京：北京大学， 2013 ．

Roychaudhuri R , YANG M , Hoshi M M , et al . Amyloid beta-protein assembly and Alzheimer disease [J]. J Biol Chem , 2009 , 284 ( 8 ): 47 - 49 .

Yankner B A , LU T . Amyloid beta-protein toxicity and the pathogenesis of Alzheimer disease [J]. J Biol Chem , 2009 , 284 ( 8 ): 47 - 55 .

Schönthal A H . Endoplasmic reticulum stress: its role in disease and novel prospects for therapy [J]. Scientifica , 2012 , 212 ( 12 ): 1 - 26 .

ZHANG Q , LIU J , CHEN S , et al . Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress [J]. Apoptosis , 2016 , 21 ( 4 ): 432 - 442 .

ZHANG X Y , ZHANG T T , SONG D D , et al . Endoplasmic reticulum chaperone GRP78 is involved in autophagy activation induced by ischemic preconditioning in neural cells [J]. Mol Brain , 2015 , 8 ( 20 ): 1 - 12 .

Meares G P , Mines M A , Beurel E , et al . Jope RSGlycogen synthase kinase-3 regulates endoplasmic reticulum (ER) stress-induced CHOP expression in neuronal cells [J]. Exp Cell Res , 2011 , 317 ( 11 ): 1621 - 1628 .

段冷昕，高杨，吴欣芳，等．蚯蚓活性组分对内质网应激所致肝细胞凋亡的保护作用研究 [J]．中国中药杂志， 2018 ， 43 ( 14 )： 2973 - 2978 ．

Badiola N , Penas C , Miñano-Molina A , et al . Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12 [J]. Cell Death Dis , 2011 , 2 ( 4 ): 149 - 152 .

Cano-González A , Mauro-Lizcano M , Iglesias-Serret D , et al . Involvement of both Caspase-8 and Noxa-activated pathways in endoplasmic reticulum stress-induced apoptosis in triple-negative breast tumor cells [J]. Cell Death Dis , 2018 , 9 ( 8 ): 134 - 136 .

Adamopoulos C , Farmaki E , Spilioti E , et al . Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells [J]. Clin Chem Lab Med , 2014 , 52 ( 6 ): 151 - 160 .

TIAN N X , GAO Y B , WANG X L , et al . Emodin mitigates podocytes apoptosis induced by endoplasmic reticulum stress through the inhibition of the PERK pathway in diabetic nephropathy [J]. Drug Des Devel Ther , 2018 , 12 : 2195 - 2211 .

杨植媛．黑逍遥散对阿尔兹海默病模型大鼠海马组织Aβ代谢相关靶点影响 [D]．兰州：甘肃中医学院， 2014 ．

吴小明，朱美香，李如辉．肝肾二脏与抗衰老的关系探讨 [J]．甘肃中医， 2004 ， 17 ( 3 )： 3 - 5 ．

吴红彦，王彩霞．黑逍遥散对AD小鼠脑组织AchE，ChAT，MAO活性的影响 [J]．甘肃中医学院学报， 2010 ， 27 ( 2 )： 23 - 25 ．

吴红彦，王彩霞．黑逍遥散对AD小鼠学习记忆及抗氧化能力的影响 [J]．甘肃中医药大学学报， 2010 ， 27 ( 1 )： 9 - 12 ．

杨长生，吴红彦，李海龙，等．黑逍遥散对阿尔茨海默病模型大鼠行为学及血清肿瘤坏死因子α及白细胞介素-6和-1β的影响 [J]．西部中医药， 2015 ， 28 ( 2 )： 10 - 12 ．

吴红彦，王虎平，王彩霞．黑逍遥散对老年性痴呆的防治作用及其机制研究 [J]．时珍国医国药， 2011 ， 22 ( 4 )： 912 - 913 ．

吴红彦，李海龙，张芸，等．黑逍遥散含药血清对Aβ25～35诱导阿尔茨海默病细胞模型的影响 [J]．中国老年学杂志， 2015 ( 1 )： 137 - 139 ．

吴红彦，邓健男，李海龙，等．黑逍遥散含药血清对PC12两种AD模型的LDH、T-SOD、MDA的影响 [J]．云南中医中药杂志， 2014 ， 35 ( 9 )： 75 - 77 ．

吴红彦，李海龙，顾静，等．黑逍遥散对Aβ-(25～35)诱导AD模型大鼠脑组织神经递质及海马病理改变的影响 [J]．中国老年学杂志， 2015 ， 35 ( 16 )： 4417 - 4420 ．

李海龙．黑逍遥散对阿尔茨海默病大鼠海马基因表达谱的影响 [J]．中国中西医结合杂志， 2016 ， 36 ( 11 )： 1345 - 1351 ．

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