高热量饮食和年龄对载脂蛋白E基因敲除小鼠脑功能的影响  

Effects of high-calorie diet and age on brain function in ApoE^(-/-) mice

作　　者：丁琳琳 郑晓清 李惠红 陶大梅 魏伟 薛偕华 Ding Linlin;Zheng Xiaoqing;Li Huihong;Tao Damei;Wei Wei;Xue Xiehua(College of Rehabilitation Medicine,Fujian University of Chinese Medicine,Fuzhou 350122,Fujian Province,China)

机构地区：[1]福建中医药大学康复医学院,福州350122 [2]福建中医药大学附属康复医院脑病一科福建省认知功能康复重点实验室

出　　处：《中华老年心脑血管病杂志》2024年第7期829-834,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(82274620);福建省自然科学基金(2021J01957);福建省卫生健康科研项目中医基础研究项目(2021zyyj69)。

摘　　要：目的探讨高热量饮食和年龄对载脂蛋白E基因敲除(ApoE^(-/-))小鼠脑功能的影响。方法选取8月龄成年ApoE^(-/-)小鼠和18月龄老年ApoE^(-/-)小鼠共20只,随机分为正常饮食成年组、正常饮食老年组、高热量饮食成年组、高热量饮食老年组,每组5只。正常饮食成年组、正常饮食老年组小鼠喂食实验室标准饲料,高热量饮食成年组、高热量饮食老年组小鼠喂食高脂饲料,干预8周。用体质量监测和葡萄糖耐量实验测试小鼠体质量、血糖变化,核磁共振波谱检测海马和下丘脑N-乙酰天冬氨酸(NAA)、胆碱(Cho)含量,Y迷宫和旷场实验检测认知功能,Western blot检测脑组织突触体相关蛋白25(SNAP-25)、突触素(synaptophysin)、突触后致密蛋白95(PSD-95)、诱导型一氧化氮合酶(iNOS)、白细胞介素1β(IL-1β)表达。结果与正常饮食成年组比较,高热量饮食成年组海马NAA、下丘脑Cho和NAA、自发交替率、SNAP-25、synaptophysin、PSD-95表达降低,差异有统计学意义(P<0.05,P<0.01),iNOS、IL-1β表达升高,差异有统计学意义(P<0.01);与正常饮食成年组比较,正常饮食老年组海马NAA、下丘脑Cho、SNAP-25、synaptophysin、PSD-95表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(P<0.01);与正常饮食老年组比较,高热量饮食老年组海马和下丘脑Cho和NAA、中心路程/总路程、SNAP-25、synaptophysin、PSD-95表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(P<0.01);与高热量饮食成年组比较,高热量饮食老年组海马NAA、中心路程/总路程、平均速度、synaptophysin表达降低(P<0.05,P<0.01),iNOS、IL-1β表达升高(1.61±0.10 vs 1.35±0.13,2.04±0.08 vs 1.54±0.11,P<0.05,P<0.01)。结论高热量饮食导致ApoE^(-/-)小鼠代谢障碍和神经炎症,抑制突触蛋白表达引起认知功能障碍;长期高热量饮食和年龄增加促进ApoE^(-/-)小鼠脑功能衰退。Objective To investigate the effects of high-calorie diet and age on brain function of ApoE^(-/-)mice.Methods A total of 20adult ApoE^(-/-)mice(8months old)and elderly ApoE^(-/-)mice(18months old)were randomly divided into normal diet adult group,normal diet elderly group,high-calorie diet adult group,and high-calorie diet elderly group,with 5animals in each group.The mice were fed with corresponding standard diet and high-fat diet for 8weeks.Their body mass was monitored,and blood glucose was detected with glucose tolerance test.The relative contents of NAA and Cho in the hippocampus and hypothalamus were detected by Magnetic resonance spectroscopy.Y-Maze and open field tests were performed to detect cognitive function,and Western blotting was applied to detect the expression of synaptic associated protein 25(SNAP-25),synaptophysin,postsynaptic dense protein-95(PSD-95),iNOS and IL-1β.Results Compared with the normal diet adult group,the NAA content in the hippocampus,Cho and NAA contents in the hypothalamus,spontaneous alternation rate,and expression levels of SNAP-25,synaptophysin and PSD-95in brain tissue(P<0.05,P<0.01)were decreased,and the expression of iNOS and IL-1β(P<0.01)was increased in the high-calorie diet adult group.The normal diet elderly group hadreduced contents of NAA in the hippocampus and Cho in the hypothalamus,and expression levelsof SNAP-25,synaptophysin and PSD-95(P<0.05,P<0.01),and elevated expression of iNOS andIL-1β(P<0.01)when compared with the normal diet adult group.Compared with the normal diet elderly group,high-calorie diet resulted in decreased Cho and NAA in both hippocampus and hypothalamus,central distance/total distance and down-regulation of SNAP-25,synaptophysin andPSD-95(P<0.05,P<0.01),and enhanced expression of iNOS and IL-1β(P<0.01)in the elderlymice.Compared with the high-calorie diet adult group,the high-calorie diet elderly group hadreduced NAA in hippocampus,central distance/total distance and average speed,and decreased expression of synaptophysin(P<0.05,P<0.01)

关 键 词：年龄因素 载脂蛋白E类 认知障碍 高热量饮食 代谢障碍 载脂蛋白E基因敲除(apoE^(-/-))小鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]