黄芪甲苷对阿尔茨海默病小鼠模型认知功能和脑内神经炎症的影响

李娟<sup>1; 2</sup>; 常子嵩<sup>3</sup>; 姚遥<sup>4; 5</sup>; 郑萍<sup>1</sup>; 王锐<sup>1</sup>; 王伟<sup>1</sup>; 韩欣益<sup>1</sup>; 李玮琦<sup>6*</sup>

文章摘要

李娟，常子嵩，姚遥，郑萍，王锐，王伟，韩欣益，李玮琦.黄芪甲苷对阿尔茨海默病小鼠模型认知功能和脑内神经炎症的影响[J].南京中医药大学学报(社会科学版),2018,34(6):597-601.

黄芪甲苷对阿尔茨海默病小鼠模型认知功能和脑内神经炎症的影响

Effects of Astragaloside Ⅳ on Cognitive Function and Neuroinflammation in Lipopolysaccharide Induced Alzheimer's Mice Model

DOI：

中文关键词: 关键词：黄芪甲苷阿尔茨海默病认知功能小胶质细胞神经炎症

英文关键词: Astragaloside Ⅳ Alzheimer’s disease cognitive function microglia neuroinflammation

基金项目:

作者	单位
李娟^1，2，常子嵩³，姚遥^4，5，郑萍¹，王锐¹，王伟¹，韩欣益¹，李玮琦^6*	1.宁夏医科大学药学院，宁夏银川 750004；2.宁夏回药现代化工程技术研究中心，宁夏银川 750004；3.天津欧德莱生物医药科技有限公司，天津 300457；4.宁夏医科大学基础医学院，宁夏银川 750004；5.宁夏医科大学回医药现代化省部共建教育部重点实验室，宁夏银川 750004；6.中国生物技术发展中心，北京 100039

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中文摘要:

目的研究黄芪甲苷对阿尔茨海默病（AD）小鼠模型的治疗作用及其神经炎症相关作用机制。方法 ICR小鼠随机分为空白组、假手术组、模型组、黄芪甲苷高、中、低剂量组、阳性对照组。除空白组和假手术组外各组小鼠侧脑室注射LPS（5、3 μL/只）建立AD小鼠模型，假手术组小鼠侧脑室注射等体积生理盐水，空白组小鼠不作任何处理。造模后次日开始给药，黄芪甲苷各给药组高、中、低剂量分别为80、40、20 mg/kg，阳性对照组给予5 mg/kg多奈哌齐，每日1次，连续灌胃21 d。在造模后14~20 d，采用Morris水迷宫实验和新物体识别（NOR）实验评价各组动物的认知能力，造模后第21天取材，ELISA法检测各组小鼠脑内海马区TNF-α和IL-1β的含量，Iba-1免疫组化染色观察各组小鼠海马区小胶质细胞数量及形态的变化。结果侧脑室注射LPS能明显损伤AD小鼠的空间学习记忆能力和新物体识别能力，使小鼠脑内海马区炎症因子TNF-α和IL-1β的含量显著升高，并使小鼠脑内海马区小胶质细胞数量增多，胞体增大，突起增粗、变短，呈现明显的活化状态。黄芪甲苷各剂量组给药可缓解LPS造成的认知功能损伤，同时明显降低AD小鼠脑内海马区TNF-α、IL-1β的含量，减少小鼠海马区小胶质细胞的数量，抑制小胶质细胞活化。结论黄芪甲苷可能通过抑制小胶质细胞活化介导的神经炎症反应来改善AD小鼠的学习记忆功能。

英文摘要:

OBJECTIVE This study aimed to investigate the effect and possible impact mechanism of Astragaloside Ⅳ on memory deficit of lipopolysaccharide (LPS) induced Alzheimer’s disease model mice. METHODS The AD model was established by intracerebroventricular injection of LPS. Different doses of Astragaloside Ⅳ (80， 40， or 20 mg/kg) were orally administered once a day. 14 days after the LPS injection， behavioral experiments including Morris water maze test and novel object recognition (NOR) test were performed to exam mice’s learning and memory abilities. 21 days after the LPS injection， the levels of TNF-α、IL-1β in hippocampus were evaluated by ELISA. The morphology and number of microglial cells were assessed by Iba-1 immunohistochemistry experiment. RESULTS Results of behavioral experiments showed that LPS injection could significantly impair cognitive function of AD mice， and Astragaloside Ⅳ administration could remarkably relieve the impairment. The levels of TNF-α and IL-1β were increased after LPS injection， while Astragaloside Ⅳ could remarkably reduce the concentrations of these inflammatory factors. Furthermore， Iba-1 immunostaining for microglia revealed that the activation of microglia induced by LPS were significantly inhibited by Astragaloside Ⅳ CONCLUSION These results indicate that Astragaloside Ⅳ could ameliorate learning and memory impairment induced by LPS and this effect was found to be mediated through inhibition of microglial activation and neuroinflammation.

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