基于APP/PS1双转基因小鼠初探输血传播阿尔茨海默症的风险  

The risk of Alzheimer's disease transmitted by blood transfusion based on APP/PS1 double transgenic mice

作　　者：陈钟声 费章城 裴仁俊 谯从超 王宗奎[1] 叶生亮[1] 马莉[1] 张容[1] 李长清[1] 杜晞[1] 曹海军[1] CHEN Zhongsheng;FEI Zhangcheng;PEI Renjun;QIAO Congchao;WANG Zongkui;YE Shengliang;MA Li;ZHANG Rong;LI Changqing;DU Xi;CAO Haijun(Institute of Blood Transfusion,Chinese Academy of Medical Sciences&Peking Union Medical College,Chengdu 610052,China)

机构地区：[1]中国医学科学院北京协和医学院输血研究所,四川成都610052

出　　处：《中国输血杂志》2023年第5期396-403,共8页Chinese Journal of Blood Transfusion

基　　金：四川省科技计划重点研发项目(2019YFS0105);中央高校基本科研业务费项目(3332018126);中国医学科学院医学与健康科技创新工程重大协同创新项目(2021-I2M-1-060)。

摘　　要：目的初探输血传播阿尔茨海默病(alzheimer disease,AD)的风险。方法3、6、9月龄APP/PS1小鼠各10只,雌雄各半,认知行为学能力测定,同龄C57小鼠作对照;采集上述尚未出现行为学改变的最大月龄APP/PS1小鼠血液,检测Aβ_(40)、Aβ_(42)含量后备用。制备Aβ_(40)、Aβ_(42)聚合物,免疫印迹分析后备用。6~7月龄昆明小鼠随机分为6组(10只/组,雌雄各半),实验组1~2尾静脉注射APP/PS1小鼠血液(100μL/只),1组为高频次注射(3次/周),2组为低频次注射(1次/周);实验组3~4注射Aβ_(40)、Aβ_(42)聚合后混合物(100μL/只),分别为高、低频次注射,具体同上;对照组1~2注射等量生理盐水,分别为高、低频次注射。上述组别注射均持续4周,注射完毕1周后进行认知行为学能力检测及分析,最后检测昆明小鼠血液Aβ_(40)、Aβ_(42)含量。结果3、6月龄APP/PS1小鼠未出现认知行为能力改变,9月龄APP/PS1小鼠出现认知行为能力改变。6~7月龄APP/PS1小鼠血液中Aβ_(40)、Aβ_(42)含量(pg/mL)分别为418.40±2.18、15.68±0.20。所制备Aβ_(40)、Aβ_(42)聚合后混合物除单体外,多为二、三聚体。无论是高频,还是低频,输注APP/PS1小鼠血液的昆明小鼠(实验组1~2)与对照组相比,在旷场试验和条件恐惧试验中出现一定焦虑样行为和短期记忆缩短,但无显著差异;其它实验组(实验组3~4)与对照组相比,在旷场试验、新物体识别、巴恩斯迷宫、条件恐惧认知行为学分析中无明显区别。ELISA检测所有实验及对照组的昆明小鼠血液Aβ_(40)、Aβ_(42)含量(pg/mL)为10.30±0.08、3.360±0.005,组间差异不明显。结论输注APP/PS1小鼠血液及Aβ_(40)、Aβ_(42)聚合后混合物对健康昆明小鼠认知功能在短期内无明显影响,AD传播风险较小。Objective To explore the risk of Alzheimer's disease(AD)transmitted by blood transfusion.Methods There were 10 APP/PS1 mice of 3,6 and 9 months old,half female and half male,and the cognitive and behavioral abilities of C57 mice of the same age were measured,and the blood of the oldest APP/PS1 mice with no behavioral changes were collected to detect the contents of Aβ_(40) and Aβ_(42).The polymers Aβ_(40) and Aβ_(42) were prepared and Western blotting analysis was conducted.Kunming mice aged from 6 to 7 months were randomly divided into 6 groups(10 mice/group,half male and half female).The blood of APP/PS1 mice was injected intravenously in experimental group 1-2(100μL/mouse)with high frequency injection(3 times/week)and low frequency injection(1 time/week),respectively.In experimental group 3-4,Aβ_(40) and Aβ_(42) polymerized mixture(100μL/mouse)were injected in high frequency and low frequency,respectively.The control group 1-2 was injected with the same amount of normal saline,with high frequency and low frequency,respectively.The above groups were injected for 4 weeks,and the cognitive and behavioral abilities were tested and analyzed one week after injection.Finally,the contents of Aβ_(40) and Aβ_(42) in blood of Kunming mice were detected.Results Change in cognitive and behavioral ability showed in 9 months old APP/PS1 mice,but not in 3 and 6 months old APP/PS1 mice.The contents of Aβ_(40) and Aβ_(42)(pg/mL)in blood of 6-7 months old APP/PS1 mice were 418.40±2.18 and 15.68±0.20,respectively.Except for monomers,most of the polymerized mixtures of Aβ_(40) and Aβ_(42) were dimers and trimers.In both high frequency and low frequency,Kunming mice transfused with blood of APP/PS1 mice(experimental group 1-2)showed a certain degree of anxiety-like behavior and short-term memory shortening in openfield test and conditioned fear test,but without significant difference.There was no significant difference in open field test,new object recognition,Barnes maze and cognitive behavior analysis of condition

关 键 词：阿尔兹海默病 APP/PS1小鼠 Β-淀粉样蛋白 输血 认知功能 

分 类 号：R457.1[医药卫生—治疗学] R592[医药卫生—临床医学] Q781[生物学—分子生物学]