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

作　　者：李娟[1,2] 姚遥 韩怀钦[3] 李玮琦[5] 李南[1] 苗珍花[3] 李遇春[1] 赵启跃 LI Juan;YAO Yao;HAN Huai-qin;LI Wei-qi;LI Nan;MIAO Zhen-hua;LI Yu-chun;ZHAO Qi-yue(School of Pharmacy,Ningxia Medical University,Yinchuan 750004,China;Ningxia Engineering and Technology Research Center for Modernization of Hui Medicine,Yinchttan 750004,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;Affiliated Hospital of Yan'an University,Yan'an 716000,China)

机构地区：[1]宁夏医科大学药学院,银川750004 [2]宁夏回药现代化工程技术研究中心,银川750004 [3]宁夏医科大学基础医学院,银川750004 [4]宁夏医科大学回医药现代化省部共建教育部重点实验室,银川750004 [5]中国生物技术发展中心,北京100039 [6]延安大学附属医院,陕西延安716000

出　　处：《中国实验方剂学杂志》2018年第24期134-139,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：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)

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。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 72ICR mice were randomly divided into six groups:normal control group,model group,matrine groups (high,medium,low dose)and positive control group.Lipopolysaccharide (LPS,5g·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 (40,20,10mg·kg^-1)and 5mg·kg^-1donepezil respectively for 21d,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-lβ (IL-lβ)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,TNF-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-1βand 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 m

关 键 词：苦参碱 阿尔茨海默病 烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶 神经炎症 

分 类 号：R20[医药卫生—中医学] R22