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

李娟; 姚遥; 韩怀钦; 李玮琦; 李南; 苗珍花; 李遇春; 赵启跃

doi:10.13422/j.cnki.syfjx.20182430

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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

药理 | 更新时间：2024-09-23

- 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
- Effect of Matrine on Learning and Memory Function and Neuroinflammation in LPS-induced Alzheimer's Disease Mice Model
- 中国实验方剂学杂志 2018年24卷第24期页码：134-139
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金项目（81460665，81660673）;宁夏高等学校科学研究项目（NGY2015097）;教育部春晖计划项目（Z2016047）;大学生创新创业训练计划项目（201510752005，NXCX2016137）
- DOI：10.13422/j.cnki.syfjx.20182430
  中图分类号： R-332;R285.5
- 纸质出版日期：2018
- 稿件说明：
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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.

Li Juan, YAO Yao, HAN Huai-qin, et al. Effect of Matrine on Learning and Memory Function and Neuroinflammation in LPS-induced Alzheimer's Disease Mice Model[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(24): 134-139.
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. DOI： 10.13422/j.cnki.syfjx.20182430.

Li Juan, YAO Yao, HAN Huai-qin, et al. Effect of Matrine on Learning and Memory Function and Neuroinflammation in LPS-induced Alzheimer's Disease Mice Model[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(24): 134-139. DOI： 10.13422/j.cnki.syfjx.20182430.

摘要

目的：研究苦参碱对阿尔茨海默病（Alzheimer's disease，AD）模型小鼠学习记忆损伤的治疗作用并探讨其可能的作用机制。方法： ICR小鼠随机分为正常组、模型组、苦参碱高、中、低剂量组和阳性药组。除正常组之外其余各组小鼠侧脑室注射脂多糖（lipopolysaccharide，LPS）建立AD小鼠模型，正常组小鼠注射等量生理盐水。之后连续灌胃给药21 d，每天1次，其中苦参碱各给药组高、中、低剂量分别为40，20，10 mg·kg-1，阳性药多奈哌齐剂量为5 mg·kg-1。采用新物体识别（novel object recognition，NOR）实验

Y迷宫实验评价各组动物的学习记忆能力；酶联免疫吸附测定（ELISA）检测各组小鼠脑内海马组织中炎症因子肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α），白细胞介素-1β（interleukin-1β，IL-1β）和活性氧（reactive oxygen species，ROS）的含量；蛋白免疫印迹法（Western blot）检测各组小鼠脑内海马区烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶亚基gp91phox，p47phox蛋白的含量。结果：与正常组比较，模型组小鼠的新物体偏爱指数和自发交替反应率明显降低（P<0.01），海马组织中TNF-α，IL-1β和ROS的含量明显升高（P<0.01），NADPH氧化酶亚基gp91phox，p47phox蛋白的表达明显升高（P<0.01）。与模型组比较，苦参碱高、中、低剂量组均可使小鼠的新物体偏爱指数和自发交替反应率明显升高（P<0.05，P<0.01），明显改善AD小鼠的学习记忆能力；同时，苦参碱各剂量组可显著降低AD模型小鼠海马组织中TNF-α，IL-1β和ROS的含量（P<0.05，P<0.01），并下调NADPH氧化酶亚基gp91phox，p47phox蛋白的表达（P<0.05，P<0.01）。结论：苦参碱可缓解LPS诱导的学习记忆功能损伤和脑内神经炎症，这些作用可能是通过抑制NADPH氧化酶亚基gp91phox和p47phox的蛋白表达来发挥的。

Abstract

Objective: To study the effects of matrine on learning and memory function and neuroinflammation in Alzheimer's disease (AD) mice model

and explore its possible mechanism of action. Method: The 72 ICR mice were randomly divided into six groups:normal control group

model group

matrine groups (high

medium

low dose) and positive control group. Lipopolysaccharide (LPS

5 g·L-1) was injected intracerebroventricularly to establish AD mouse model

while normal control group mice were injected with the same volume of normal saline. Afterwards

matrine groups and positive control group were orally administered with different doses of matrine (40

10 mg·kg-1) and 5 mg·kg-1 donepezil respectively for 21 d

once a day; while the normal control group and model group were given with normal saline instead.The learning and memory abilities of the mice were assessed by novel object recognition (NOR) test and Y maze test. The levels of tumor necrosis factor-α (TNF-α)

interleukin-1β (IL-1β) and reactive oxygen species (ROS) in mice hippocampus were detected by enzyme linked immunosorbent assay (ELISA). The protein expression levels of nicotinamide adenine dinucleotide phosphate(NADPH) oxidase subunits gp91phox and p47phox were detected by Western blot analysis. Result: As compared with the normal control group

LPS injection could remarkably reduce the novel object preference index and spontaneous alternation behavior (P<0.01)

increase the contents of TNF-α

IL-1β and ROS (P<0.01)

and up-regulate protein expression of NADPH oxidase subunits gp91phox and p47phox (P<0.01). As compared with the model group

matrine high

middle and low doses could significantly increase the novel object preference index and spontaneous alternation behavior (P<0.05

P<0.01)

reduce the levels of TNF-α

IL-1β and ROS (P<0.05

P<0.01)

and down-regulate the protein expression of gp91phox and p47phox (P<0.05

P<0.01). Conclusion: Matrine could relieve the impairment of learning and memory function and neuroinflammation induced by LPS injection

and these effects may be mediated through inhibition of NADPH oxidase subunits gp91phox and p47phox expression in hippocampal tissue.

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