腺苷A1受体拮抗剂的长期干预对阿尔茨海默病模型小鼠认知功能的影响  

Effects of Long-term Intervention of Adenosine A1 Receptor Antagonist on Cognitive Function in Alzheimer’s Disease Model Mice

作　　者：耿雨梅 焦利武 刘旭阳 舒凯[2] 康慧聪[1] Geng Yumei;Jiao Liwu;Liu Xuyang(Department of Neurology,Tongji Hospital,Tongji Medical College Huazhong University of Science and Technology,Wuhan 430030,China;Department of Neurosurgery,Tongji Hospital,Tongji Medical College Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030 [2]华中科技大学同济医学院附属同济医院神经外科,武汉430030

出　　处：《华中科技大学学报（医学版）》2024年第2期141-147,共7页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81974279);湖北省自然科学基金资助项目(No.2022CFB279)。

摘　　要：目的探讨腺苷A1受体拮抗剂DPCPX的长期干预对阿尔茨海默病(Alzheimer’sdisease,AD)模型小鼠认知功能相关电生理指标、行为学表现及病理标志物的影响。方法使用7月龄C57BL/6J及APP/PS1小鼠,随机分为C57-对照组、C57-DPCPX组、APP/PS1-对照组及APP/PS1-DPCPX组,分别采用DPCPX(1mg/kg·d)或对照溶剂连续腹腔注射21d。采用Plexon系统记录小鼠海马CA1区局部场电位,MATLAB软件评估海马认知功能相关电生理指标——尖波涟漪(sharpwaveripples,SWRs)的特征,Morris水迷宫实验评估小鼠的空间记忆能力,免疫荧光染色检测海马内Aβ斑块沉积。结果分析4组小鼠认知功能相关电生理指标(SWRs)、行为学表现(Morris水迷宫)及脑组织Aβ检测结果发现:①在SWRs的平均数量及平均持续时间上,C57-对照组与C57-DPCPX组之间,APP/PS1-对照组与APP/PS1-DPCPX组之间差异均无统计学意义(均P>0.05),仅C57-对照组显著多于APP/PS1-对照组(P=0.0019,P=0.0202)。②Morris水迷宫实验中,在学习阶段的逃避潜伏期上,C57-对照组与C57-DPCPX组之间,APP/PS1-对照组与APP/PS1-DPCPX组之间差异均无统计学意义(均P>0.05),仅C57-对照组与APP/PS1-对照组相比显著缩短(P<0.05)。在探索阶段,在穿越平台次数及目标象限停留时间占比上,C57-对照组与C57-DPCPX组之间,APP/PS1-对照组与APP/PS1-DPCPX组之间差异均无统计学意义(均P>0.05),仅C57-对照组显著多于APP/PS1-对照组(P=0.0024,P=0.0415)。③在Aβ斑块的数量及面积上,APP/PS1-对照组与APP/PS1-DPCPX组相比差异均无统计学意义(均P>0.05)。结论腺苷A1受体拮抗剂DPCPX的长期干预不能显著改善AD模型小鼠的认知功能,提示对于AD这一具有复杂发病机制的疾病,仅针对单一靶点的干预很难达到显著改善认知功能的作用。Objective To investigate the effects of long-term intervention of adenosine A1 receptor antagonist DPCPX on cognitive function related electrophysiological indexes,behavioral performance and pathological examination in Alzheimer's disease(AD)model mice.Methods Seven-month-old C57BL/6J and APP/PS1 mice were randomly divided into C57-control group,C57-DPCPX group,APP/PS1-control group and APP/PS1-DPCPX group.DPCPX(1 mg/kg·d)or control vehicle was injected intraperitoneally for 21 consecutive days.The Plexon system was used to record local field potential in the hippocampus CA1 region of mice.MATLAB software was used to evaluate the characteristics of sharp wave ripples(SWRs),which were a type of electrophysiological index related to hippocampal cognitive function.Morris water maze was used to evaluate the spatial memory ability of mice.Immunofluorescence staining was used to detect Aβplaque deposition in the hippocampus.Results The cognitive function related electrophysiological indexes(SWRs),behavioral performance(Morris water maze)and Aβpathological examination of the four groups of mice were analyzed.The results were as follows:(1)As for the average number and average duration of SWRs,there was no significant differences between the C57-control group and the C57-DPCPX group,and between the APP/PS1-control group and the APP/PS1-DPCPX group(both P>0.05),only the results in C57-control group were significantly higher than those in APP/PS1-control group(P=0.0019,P=0.0202).(2)In Morris water maze experiment,there was no significant difference in escape latency during learning phase between the C57-control group and the C57-DPCPX group mice,and between the APP/PS1-control group and the APP/PS1-DPCPX group(both P>0.05),only the results in C57-control group were significantly shorter than those in APP/PS1-control group(P<0.05).In the exploration stage,no statistical difference was found in the platform crossing times and the target quadrant residence time ratio between the C57-control group and the C57-DPCPX group,an

关 键 词：阿尔茨海默病 腺苷A1受体 尖波涟漪 认知功能 局部场电位 

分 类 号：R749.16[医药卫生—神经病学与精神病学]