黄精丸对阿尔茨海默病大鼠大脑的抗氧化作用及A<italic style="font-style: italic">β</italic><sub>1-42</sub>，APP蛋白表达的影响

杨晶莹; 肖移生; 姜劼琳; 高萌; 侯吉华

doi:10.13422/j.cnki.syfjx.20200305

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黄精丸对阿尔茨海默病大鼠大脑的抗氧化作用及Aβ_1-42，APP蛋白表达的影响

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- 黄精丸对阿尔茨海默病大鼠大脑的抗氧化作用及Aβ_1-42，APP蛋白表达的影响
- Effect of Huangjingwan on Antioxidant Functions and Aβ_1-42 and APP Protein Expressions in Brain of Alzheimer' s Disease Rats
- 中国实验方剂学杂志 2020年26卷第6期页码：32-38
- 作者机构：
  
  1.江西中医药大学，南昌　 330004
  2.江西中医药大学　中医学院，生命科学院，南昌　 330004
- 作者简介：
  
  [第一作者]　杨晶莹，在读硕士，从事中药神经保护研究，Tel：0791-87118907, E-mail: 1025621996@qq.com
  *肖移生，硕士，副教授，从事中药神经保护研究，Tel：0791-7118907, E-mail: xys760928@sina.com
- 基金信息：
  
  2018年江西省卫生健康委中医药科研计划课题(2018B014);江西中医药大学双一流学科建设科研项目(2019SYLXK038)
- DOI：10.13422/j.cnki.syfjx.20200305
  中图分类号： R2-0; R22; R285.5; R289
- 收稿日期：2019-07-17，
  
  网络出版日期：2019-10-17，
  
  纸质出版日期：2020-03-20
- 稿件说明：
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杨晶莹, 肖移生, 姜劼琳, 等. 黄精丸对阿尔茨海默病大鼠大脑的抗氧化作用及Aβ_1-42，APP蛋白表达的影响[J]. 中国实验方剂学杂志, 2020,26(6):32-38.

Jing-ying YANG, Yi-sheng XIAO, Jie-lin JIANG, et al. Effect of Huangjingwan on Antioxidant Functions and Aβ_1-42 and APP Protein Expressions in Brain of Alzheimer' s Disease Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(6): 32-38.
杨晶莹, 肖移生, 姜劼琳, 等. 黄精丸对阿尔茨海默病大鼠大脑的抗氧化作用及Aβ_1-42，APP蛋白表达的影响[J]. 中国实验方剂学杂志, 2020,26(6):32-38. DOI： 10.13422/j.cnki.syfjx.20200305.

Jing-ying YANG, Yi-sheng XIAO, Jie-lin JIANG, et al. Effect of Huangjingwan on Antioxidant Functions and Aβ_1-42 and APP Protein Expressions in Brain of Alzheimer' s Disease Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(6): 32-38. DOI： 10.13422/j.cnki.syfjx.20200305.

摘要

目的：

探讨黄精丸药方(Huangjingwan，HW)对阿尔茨海默病(AD)大鼠大脑的抗氧化作用及

-淀粉样多肽1-42(A

1-42

)，淀粉样前体蛋白(APP)表达的影响。

方法：

SD大鼠随机分成正常组，假手术组，AD模型组，HW低、中、高剂量组(相当药丸剂量1，3，9 g·kg

-1

·d

-1

组)。给大鼠腹腔注射1.25%

-半乳糖液(120 mg·kg

-1

·d

-1

，连续6周)后，再右侧脑室一次性注射A

1-42

10 μg，制作大鼠AD模型；造模2周后各药物组大鼠灌胃相应剂量试验药物，假手术组及AD模型组大鼠灌胃给生理盐水1 mL，每天1次。灌胃持续8周。采用跳台实验评价各大鼠的学习记忆能力；体质量10%的负荷游泳实验测试各大鼠的体能耐力变化；比色法检测各大鼠大脑组织超氧化物歧化酶(SOD)，谷胱甘肽还原酶(GR)，谷胱甘肽过氧化物酶(GSH-Px)抗氧化酶系活性，谷胱甘肽(GSH)与丙二醛(MDA)含量变化；酶联免疫吸附测定(ELISA)检测各大鼠大脑组织白细胞介素-1

(IL-1

)，肿瘤坏死因子-

(TNF-

)，A

1-42

与APP蛋白含量变化；蛋白免疫印迹法(Western blot)检测各大鼠大脑APP蛋白表达变化。

结果：

与正常组比较，AD模型组大鼠表现出明显的痴呆状态，少动易呆卧，学习反应时间延长，学习记忆错误次数显著增多，体能衰减明显，大脑内抗氧化酶(SOD，GR，GSH-Px)活性及抗炎因子GSH水平显著降低，炎症因子MDA，IL-1

，TNF-

水平显著升高，A

1-42

蛋白含量显著升高，APP蛋白含量显著下降(

0.01)。与AD模型组比较，HW低、中、高剂量均可改善AD大鼠的痴呆症状，提高学习记忆成绩，改善机体虚弱、提高体能，升高大脑内SOD，GR，GSH-Px活性及抗炎因子GSH水平，降低MDA，IL-1

，TNF-

水平，并能降低大脑内A

1-42

及升高APP蛋白水平(

0.05，

0.01)；且1～9 g·kg

-1

·d

-1

剂量范围内的HW，随剂量增加，药效作用越明显。

结论：

HW有防治AD的功能，这一作用与HW可以增强脑内抗氧化系统功能、降低神经炎症反应、降低氧化应激引发的A

1-42

沉积、维持APP蛋白表达水平等有关。

Abstract

Objective:

To observe the effect of Huangjingwan (HW) on antioxidant functions and

-amyloid 1-42 (A

1-42

) and amyloid precursor protein (APP) expressions in the brain of Alzheimer' s disease (AD) rats.

Method:

SD rats were randomly divided into normal control group

sham model control group

AD model group

and low

medium

high-dose (equivalent raw drug dose 1

9 g·kg

-1

·d

-1

) HW groups.The AD models were established through intraperitoneal injection with 1.25%

-galactose (120 mg·kg

-1

·d

-1

6 consecutive weeks) and then one-time right ventricular injection with A

1-42

(10 μg). Two weeks after modeling

the rats in each HW group received corresponding drugs through intragastric administration

once a day

while the rats in sham model control group

AD model group were given normal saline 1 mL through intragastric administration

once a day.Gastric perfusion lasted for 8 weeks.At the end of the experiment

learning and memory abilities of the rats were assessed by Platform Jumping Test.The changes of physical endurance in rats were tested by 10% weight swimming under load.The activities of superoxide dismutase (SOD)

glutathione reductase (GR)

glutathione peroxidase (GSH-Px) antioxidant enzymes and the contents of glutathione (GSH) and malondialdehyde (MDA) in rat brain tissue were detected by colorimetry.The changes of interleukin-1

(IL-1

)

tumor necrosis factor-

(TNF-

)

1-42

and APP protein in rat brain tissues were determined by enzyme linked immunosorbent assay (ELISA). Western blot analysis was used to measure the expression of APP protein in rat brain.

Result:

Compared with the normal control group

rats in AD model group showed an obvious dementia state

that is more lying and less movement

longer learning response time

significant increase in the number of learning and memory errors

significant attenuation in physical fitness

significant decrease in the activities of antioxidant enzymes (SOD

GSH-Px) and anti-inflammatory factors GSH in brain

significant rise in the levels of inflammatory factors MDA

IL-1

and TNF-

and the content of A

1-42

protein

and significant reduction in the content of APP protein in brain (

0.01). Low

medium and high-dose HW could ameliorate dementia symptoms in AD rats

improve the achievement of learning and memory

antagonize body weakness and increase physical fitness

promote SOD

GSH-Px activities and anti-inflammatory factor GSH level in the brain

reduce the levels of MDA

IL-1

and TNF-

in the brain

decrease the level of A

1-42

and increase the level of APP protein in the brains of AD rats compared with the AD model group (

0.05

0.01)

besides

within the dose range of 1-9 g·kg

-1

·d

-1

HW has a more obvious effect with the increase of dose.

Conclusion:

HW has the effects in preventing and treating AD

which is related to the HW' s mechanisms in enhancing the function of antioxidant system in brain

reducing neuroinflammatory reaction and deposition of A

1-42

induced by oxidative stress

and maintaining the expression level of APP protein.

关键词

Keywords

references

ALZHEIMER'S ASSOCIATION . 2018 Alzheimer's disease facts and figures [J]． Alzheimer' s Dement , 2018 , 14 ( 3 ): 367 - 429 .

黄洋，孙英新，曾妙，等．补阳还五汤及其组分治疗阿尔茨海默病的研究进展 [J]．中国实验方剂学杂志， 2019 ， 25 ( 19 ): 212 - 218 .

闫妍，韩冉，高俊峰，等．地黄引子改善AD大鼠脑组织线粒体生物合成与氧化损伤的机制 [J]．中国实验方剂学杂志， 2018 ， 24 ( 21 ): 105 - 110 .

A SINGH , R KUKRETI , L SASO , et al . Oxidative stress: a key modulator in neurodegenerative diseases [J]． Molecules , 2019 , 24 ( 8 ): E1583 .

K N PRASAD ． Oxidative stress and pro-inflammatory cytokines may act as one of the signals for regulating microRNAs expression in Alzheimer's disease [J]． Mech Ageing Dev , 2017 ， 162 : 63 - 71 .

L CHEN , C ZHANG , Y HAN , et al . Gingko biloba Extract (EGb) inhibits oxidative stress in neuro 2A cells overexpressing APPsw [J]． Biomed Res Int , 2019 , doi: 10.1155/2019/7034983 http://dx.doi.org/10.1155/2019/7034983 .

刘晓杰，杨威，祁金顺．氧化应激与阿尔茨海默病 [J]．生理学报， 2019 ， 64 ( 1 ): 87 - 95 .

王琳琳，胡镜清，张治国，等．中药及复方减少阿尔茨海默病氧化损伤研究探析 [J]．世界科学技术—中医药现代化， 2019 ， 21 ( 1 ): 38 - 43 .

魏宪纯，李明杰，张春蕾．九转黄精丸对衰老小鼠皮肤及血清中脂褐质含量影响的研究 [J]．中医药信息， 2009 ， 26 ( 6 ): 51 - 52 .

周志军，肖移生．黄精丸对大鼠大脑局灶性脑缺血损伤保护作用研究 [J]．井冈山大学学报：自然科学版， 2012 ， 33 ( 1 ): 88 - 90 .

肖移生，高萌，侯吉华．黄精地龙提取液对老年痴呆大鼠脑内烟碱型乙酰胆碱受体的影响 [J]．中国实验方剂学杂志， 2017 ， 23 ( 14 ): 140 - 145 .

苏琦，徐德恩．电针治疗对AD大鼠学习记忆能力及细胞周期蛋白P53、P21表达的影响 [J]．重庆医学， 2013 ， 42 ( 21 ): 2444 - 2448 .

黄锐，吴锋，赵健，等．电针联合天麻素对阿尔茨海默病大鼠海马CA1区沉默信息调节因子2同源蛋白1和过氧化物酶体增殖物激活受体 γ 辅激活子1 α 表达的影响 [J]．针刺研究， 2018 ， 43 ( 3 ): 140 - 145 .

G PAXINOS , C WATSON ． The Rat Brain in Stereotaxic Coordinates [M]. 7th edition . San Diego : Academic Press ， 2014 .

肖苗苗．中医药治疗阿尔茨海默病的研究进展 [J]．中医学报， 2012 ， 27 ( 5 ): 631 - 632 .

P BARAI , N RAVAL , S ACHARYA ， et al . Bergenia ciliata ameliorates streptozotocin-induced spatial memory deficits through dual cholinesterase inhibition and attenuation of oxidative stress in rats [J]． Biomed Pharmacother , 2018 , doi: 10.1016/j.biopha.2018.03.115 http://dx.doi.org/10.1016/j.biopha.2018.03.115 .

B CUI , S ZHANG , Y WANG ， et al . Farrerol attenuates β -amyloid-induced oxidative stress and inflammation through Nrf2/Keap1 pathway in a microglia cell line [J]． Biomed Pharmacother ， 2019 ， 109 : 112 - 119 .

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 .

Z S SAICIĆ , M O SIMOVIC , B KORAĆ , et al . Activity of antioxidant defense enzymes and glutathione content in some tissues of the Belgrade (b/b) laboratory rat [J]． Comp Biochem Physiol C Pharmacol Toxicol Endocrinol ， 1997 ， 117 ( 2 ): 173 - 179 .

张春蕾，李明杰，魏宪纯．九转黄精丸对衰老小鼠皮肤组织SOD活力及脂褐质含量影响的研究 [J]．黑龙江医药科学， 2008 ， 31 ( 6 ): 80 .

魏宪纯，李明杰，张春蕾．九转黄精丸对衰老小鼠皮肤组织形态学的影响 [J]．中国中医药科技， 2010 ， 17 ( 3 ): 278 .

H STEINER , A FUKUMORI , S TAGAMI ， et al . Making the final cut: pathogenic amyloid- β peptide generation by γ -secretase [J]． Cell Stress ， 2018 , 28，2 ( 11 ): 292 - 310 .

陈阳阳，孔立红，孙国杰，等． “益肾调督”针灸法对AD大鼠血清A β 及海马APP表达的影响 [J]．时珍国医国药， 2016 ， 27 ( 9 ): 2289 - 2291 .

B L TANG ． Amyloid precursor protein (APP) and GAB aergic neurotransmission [J]． Cells ， 2019 , 8 ( 6 ): E550 .

H C RICE , D D MALMAZET , A SCHREURS , et al . Secreted amyloid- β precursor protein functions as a GABA B R1a ligand to modulate synaptic transmission [J]． Science , 2019 , 363 ( 6423 ): eaao4827 .

吴燕春，包传红，阎莉，等．绞股蓝正丁醇提取物对快速老化小鼠A β 蛋白的影响 [J]．中成药， 2016 ， 38 ( 9 ): 1898 - 1902 .

J L JANKOWSKY , D J FADALE , J ANDERSON , et al . Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase [J]． Hum Mol Genet , 2004 ， 13 ( 2 ): 159 - 170 .

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黄精丸对阿尔茨海默病大鼠大脑的抗氧化作用及Aβ1-42，APP蛋白表达的影响

Effect of Huangjingwan on Antioxidant Functions and Aβ1-42 and APP Protein Expressions in Brain of Alzheimer' s Disease Rats

DOI：10.13422/j.cnki.syfjx.20200305

摘要

Abstract

关键词

Keywords

references

黄精丸对阿尔茨海默病大鼠大脑的抗氧化作用及Aβ_1-42，APP蛋白表达的影响

Effect of Huangjingwan on Antioxidant Functions and Aβ_1-42 and APP Protein Expressions in Brain of Alzheimer' s Disease Rats