探讨电针对阿尔茨海默病小鼠模型学习记忆能力的影响及作用机制

游明灿; 陈新旺; 游言文; 郝莉

doi:10.3969/j.issn.1006-2157.2023.01.022

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探讨电针对阿尔茨海默病小鼠模型学习记忆能力的影响及作用机制

针灸推拿 | 更新时间：2023-02-03

- 探讨电针对阿尔茨海默病小鼠模型学习记忆能力的影响及作用机制
- Exploring the impact and mechanisms of electroacupuncture on the ability of learning and memory in a mouse model of Alzheimer’s disease
- 北京中医药大学学报 2023年46卷第1期页码：132-140
- 作者机构：
  
  1.郑州大学第一附属医院　郑州　450052
  2.河南中医药大学第三附属医院
  3.河南中医药大学医学院
- 作者简介：
  
  游明灿，男，硕士，主治医师
  #郝莉，副教授，硕士生导师，主要研究方向：中医药防治神经退行性疾病，E-mail: haoli66@126.com
- 基金信息：
  
  国家自然科学基金青年科学基金项目(81704183);河南省科技攻关项目(202102310828;222102310280);河南省高等学校青年骨干教师培养计划项目(2019GGJS110)
- DOI：10.3969/j.issn.1006-2157.2023.01.022
  中图分类号： R246.6
- 收稿：2022-04-01，
  
  网络首发：2022-10-27，
  
  纸质出版：2023-01-30
- 稿件说明：
移动端阅览
游明灿, 陈新旺, 游言文, 等. 探讨电针对阿尔茨海默病小鼠模型学习记忆能力的影响及作用机制[J]. 北京中医药大学学报, 2023,46(1):132-140.

YOU Mingcan, CHEN Xinwang, YOU Yanwen, et al. Exploring the impact and mechanisms of electroacupuncture on the ability of learning and memory in a mouse model of Alzheimer’s disease[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(1): 132-140.
游明灿, 陈新旺, 游言文, 等. 探讨电针对阿尔茨海默病小鼠模型学习记忆能力的影响及作用机制[J]. 北京中医药大学学报, 2023,46(1):132-140. DOI： 10.3969/j.issn.1006-2157.2023.01.022.

YOU Mingcan, CHEN Xinwang, YOU Yanwen, et al. Exploring the impact and mechanisms of electroacupuncture on the ability of learning and memory in a mouse model of Alzheimer’s disease[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(1): 132-140. DOI： 10.3969/j.issn.1006-2157.2023.01.022.

摘要

目的

探讨电针对β－淀粉样蛋白25－35(Aβ

25－35

)诱导的阿尔茨海默病(AD)小鼠模型学习记忆能力和核苷酸寡聚化结构域样受体蛋白3(NLRP3)/半胱氨酸蛋白酶－1(caspase-1)通路的影响。

方法

将30只2月龄雄性C57BL/6小鼠按体质量随机分为对照组、模型组和电针组，每组10只。双侧侧脑室内立体定位注射Aβ

25－35

诱导建立AD小鼠模型。分别对对照组(侧脑室内注射无菌生理盐水)、模型组(侧脑室内注射Aβ

25－35

)和电针组(侧脑室内注射Aβ

25－35

，电针“百会”和“大椎”)进行干预。每侧侧脑室注射的Aβ

25－35

和生理盐水均为3 μL。注射1次，7 d后进行电针治疗，2个疗程，每疗程6 d(每天1次，每次15 min)，2个疗程中间休息1 d，共计治疗13 d。采用Morris水迷宫、Y迷宫和旷场实验检测各组小鼠学习记忆能力。酶联免疫吸附测定(ELISA)法检测各组小鼠海马组织白细胞介素－1β(IL-1β)和肿瘤坏死因子-α(TNF-α)表达水平。实时荧光PCR检测小鼠海马组织NLRP3、caspase-1和IL-1β的mRNA水平。蛋白质印迹法检测NLRP3、caspase-1和IL-1β蛋白表达水平。

结果

与对照组相比，模型组小鼠在Morris水迷宫的第4、5天逃避潜伏期延长(

0.05)，穿越目标象限平台次数和停留时间百分比降低(

0.05)；Y迷宫自发交替准确率下降(

0.05)；旷场中理毛次数减少(

0.05)，中心区域停留时间延长(

0.05)；海马组织内IL-1β和TNF-α蛋白表达上调(

0.05)；NLRP3、caspase-1和IL-1β的mRNA及蛋白表达水平均上调(

0.05)。与模型组相比，电针组第5天逃避潜伏期缩短(

0.05)，穿越目标象限平台次数和停留时间百分比增加(

0.05)；Y迷宫自发交替准确率上升(

0.05)；旷场中理毛次数增多(

0.05)，中心区域停留时间缩短(

0.05)；海马组织内IL-1β和TNF-α蛋白表达下调(

0.05)。NLRP3、caspase-1和IL-1β的mRNA及蛋白表达水平均下调(

0.05)。

结论

电针“百会”和“大椎”可改善Aβ

25－35

诱导建立的AD小鼠模型学习记忆能力，这可能与电针通过NLRP3/caspase-1通路减轻海马炎症反应相关。

Abstract

Objective

We aimed to investigate the effects of electroacupuncture on learning and memory and on the NOD-like receptor protein 3(NLRP3)/cysteine-aspartic proteases-1 (caspase-1) pathway in a mouse model of Alzheimer’s disease (AD) induced by Aβ

25-35

Methods

Thirty 2-month-old male C57BL/6 mice were divided into control

model

and electroacupuncture groups according to the principle of random assignment

with ten mice per group. The AD mouse model was induced by stereotaxic injection of Aβ

25-35

into the bilateral lateral ventricles. The interventions were conducted in the control group (intralateral ventricular injection of sterile saline)

model group (intralateral ventricular injection of Aβ

25-35

)

and electroacupuncture group (intralateral ventricular injection of Aβ

25-35

and electroacupuncture of GV20 and GV14) respectively. Aβ

25-35

and saline were injected into each lateral ventricle at 3 μL. One dose of injection was given and seven days later electroacupuncture was administered. Treatment was carried out for 2 sessions and 6 days per session(1 session of 15 min once per day) with 1 day of rest in between

for a total of 13 days. The Morris water maze

Y-maze

and open field experiments were performed to evaluate the learning and memory abilities of the mice in each group. The expression levels of the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the hippocampus of each group were measured by enzyme linked immunosorbent assay (ELISA). The mRNA levels of NLRP3

caspase-1

and IL-1β in the hippocampus of mice were analyzed by real-time PCR. The protein expression of NLRP3

caspase-1

and IL-1β was investigated with Western blotting.

Results

Compared to the control group

the mice in the model group had a prolonged escape latency on Day 4 and 5 of the Morris water maze (

0.05) and a reduced number of platform crossings and percentage of time spent in the target quadrant (

0.05). The spontaneous alternation accuracy of the mice in the Y-maze was significantly reduced (

0.05). Mice in the open field test had a remarkably lower number of grooming incidents (

0.05) and spent more time in the central area (

0.05). The expression of inflammatory factors IL-1β and TNF-α was elevated in the hippocampal tissue of the model group by ELISA (

0.05). The mRNA and protein expression of NLRP3

Caspase-1 and IL-1β were upregulated in the model group (

0.05). Compared to the model group

the mice in the electroacupuncture group had a shorter escape latency on Day 5 of the Morris water maze (

0.05)

an increased number of platform crossings and percentage of time spent in the target quadrant (

0.05)

improved accuracy of spontaneous alternation in the Y-maze (

0.05)

a higher number of grooming incidents in the open field (

0.05)

and a shorter time spent in the central area (

0.05). The expression of IL-1β and TNF-α was reduced in the hippocampal tissue of the electroacupuncture group(

0.05). The mRNA and protein expression of NLRP3

Caspase-1

and IL-1β were all downregulated in the electroacupuncture group (

0.05).

Conclusion

Electroacupuncture at the GV20 and GV14 acupuncture points enhanced learning and memory in the Aβ

25-35

-induced AD mouse model

which may be related to the alleviation of hippocampal inflammatory responses by electroacupuncture via the NLRP3/caspase-1 pathway.

关键词

Keywords

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