自主性运动对β淀粉样蛋白25-35诱导的小鼠学习记忆损伤的早期影响  

Early influence of voluntary exercise against impairment of learning and memory function in mice induced by β-amyloid peptide 25-35

作　　者：汪琴[1] 王蔚[1] 丁新生[1] 单春雷[2] 乔莉[3] 孙建国[1] 李敏[1] 燕兰云[1] 沈飞飞[1] 吴婷[1] 

机构地区：[1]南京医科大学第一附属医院神经内科,210029 [2]南京医科大学第一附属医院康复科,210029 [3]南京医科大学第一附属医院急诊科,210029

出　　处：《中华神经科杂志》2013年第9期609-613,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目（30901578）;江苏省卫生厅＂科教兴卫工程＂重点人才项目（RC2011072）;江苏省＂六大人才高峰＂第八批高层次人才资助项目（2011-WS-031）;江苏省高校＂青蓝工程＂中青年学术带头人培养对象项目（JX2161015003）

摘　　要：目的 观察自主性运动对小鼠散发性阿尔茨海默病学习记忆损伤的早期影响及其影响途径.方法 将24只雄性C57bl/6小鼠[体重（22.5±2.5）g]采用随机数字表法完全随机分为对照组、运动对照组、模型组和治疗组,每组各6只.采用侧脑室注射β淀粉样蛋白25-35（Aβ25-35）制备散发性阿尔茨海默病模型,运动对照组和治疗组进行12 d的自主性运动,对照组和模型组不进行运动.采用Y迷宫和旷场试验分别检测小鼠短期学习记忆能力和情绪改变；HE染色观察海马CA1区神经元病理损伤情况；免疫组织化学染色检测海马区胶质炎性反应.结果 模型组较对照组小鼠短期记忆能力明显下降（进臂正确率：52.60±1.46,65.50±2.78,t =4.111,P=0.003）,治疗组与模型组相比,进臂正确率有显著提升（58.57±2.17,52.60±1.46,t=-2.385,P=0.044）；与对照组相比,模型组海马CA1区深染的神经细胞比例（％）明显增加（5.11±0.57,2.52±0.52,t=-4.894,P=0.003）.另外,海马区星形胶质细胞活化数量以及小胶质细胞数量,治疗组与模型组相比较分别下调17.86％（与对照组比值：0.99±0.13,1.17±0.10,t=2.455,P=0.036）和26.23％（与对照组比值：0.93±0.04,1.19 ±0.11,t =2.412,P=0.043）.运动对小鼠的情绪变化没有明显影响.结论 自主性运动能改善Aβ25-35小鼠海马胶质炎性反应,减轻神经细胞损伤,从而改善Aβ25-35诱导的小鼠学习记忆缺陷.Objective To investigate the early influence and the relevant pathway of voluntary exercise against impairment of learning and memory in mice with sporadic Alzheimer＇ s disease.Methods Twenty-four male C57bl/6 mice （weight （22.5 ± 2.5） g） were randomly divided into 4 groups：control group,exercise control group,model group and treatment group,6 in each group.Intracerebroventricular injection of β-amyloid peptide-25-35 （Aβ25-35） was used to make mock Alzheimer＇ s disease,and then mice in exercise control group and treatment group were allowed to exercise training for 12 days,non-exercise to control group and model group.Y-maze and open field test were arranged to measure the short-term change of learning,memory and emotions,respectively.Neuronal damage in the hippocampal CA1 region was observed by HE staining.The expression level of glial inflammatory response was quantitatively determined with method of immunohistochemistry.Results A[25_35 could cause impairment of learning and memory （accuracy in Y maze：52.60 ± 1.46,65.50 ± 2.78,t =4.111,P =0.003; ％ of dark neruons in CA1 in HE staining：5.11 ± 0.57,2.52 ± 0.52,t =-4.894,P =0.003）,and it could be significantly improved after exercise （accuracy in Y maze：58.57 ± 2.17,52.60 ± 1.46,t =-2.385,P =0.044）.Additionally,the level of activated astrocytes and microglia expression in hippocampus decreased by 17.86％ （ratio to control：0.99 ± 0.13,1.17 ± 0.10,t =2.455,P =0.036） and 26.23％ （ratio to control：0.93 ± 0.04,1.19 ± 0.11,t =2.412,P =0.043）,respectively.Conclusion Exercise plays an anti-inflammatory role in the progression of Alzheimer＇ s disease,reducing the nerve cell damage and improving learning and memory function.

关 键 词：阿尔茨海默病 淀粉样Β蛋白 运动(Exercise) 神经胶质 

分 类 号：R378.2[医药卫生—病原生物学]