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

作　　者：李娟[1,2] 常子嵩 姚遥 郑萍[1] 王锐[1] 王伟[1] 韩欣益 李玮琦 LI Juan;CHANG Zi song;YAO Yao;ZHENG Ping;WANG Rui;WANG Wei;HAN Xin yi;LI Wei qi(School of Pharmacy,Ningxia Medical University,Yinchuan,750004,China;Ningxia Engineering and Technology Research Center for Modernization of Hui Medicine,Yinchuan,750004,China;Tianjing Odrei Biomedical Technology Co.,Ltd,Tianjing,300457,China;School of Basic Medical Science,Ningxia Medical University,Yinchuan,750004,China;Key Laboratory of Hui Ethnic Medicine Modernization,Ministry of Education,Yinchuan,750004,China;;China National Center for Biotechnology Development,Beijing,100039,China)

机构地区：[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

出　　处：《南京中医药大学学报》2018年第6期597-601,共5页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：宁夏高等学校科学研究项目(NGY2015097);国家自然科学基金(81660673;81460665);宁夏回族自治区重点研发计划重点项目(2018BFG02005);教育部春晖计划项目(Z2016047);大学生创新创业训练计划项目(201510752005;20140331)

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、3μL/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、20mg/kg,阳性对照组给予5mg/kg多奈哌齐,每日1次,连续灌胃21d。在造模后14~20d,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。OBJECTIVE This study aimed to investigate the effect and possible impact mechanism of AstragalosideⅣon 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 AstragalosideⅣ(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 TNFα、IL 1βin 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 AstragalosideⅣadministration could remarkably relieve the impairment.The levels of TNFαand IL 1βwere increased after LPS injection,while AstragalosideⅣcould 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 AstragalosideⅣCONCLUSION These results indicate that AstragalosideⅣcould ameliorate learning and memory impairment induced by LPS and this effect was found to be mediated through inhibition of microglial activation and neuroinflammation.

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 

分 类 号：R285.5[医药卫生—中药学]