基于DTI和MRS探讨ApoE-/-小鼠短暂性全脑缺血后认知功能变化的机制  

Cognitive function changes of apolipoprotein E-/-mice after transient global cerebral ischemia by diffusion tensor imaging and magnetic resonance spectroscopy

作　　者：杨景达 王夏蕾 梁胜祥 魏伟 吕昕儒 陆璐 薛偕华 Yang Jingda;Wang Xialei;Liang Shengxiang;Wei Wei;Lyu Xinru;Lu Lu;Xue Xiehua(Rehabilitation Medical School of Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology,Fujian University of Traditional Chinese Medicine,Fujian Key Laboratory of Rehabilitation Technology,Fuzhou 350122,China;Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350003,China)

机构地区：[1]福建中医药大学康复医学院,福州350122 [2]福建中医药大学康复医疗技术国家地方联合工程研究中心/福建省康复技术重点实验室,福州350122 [3]福建中医药大学附属康复医院,福州350003

出　　处：《中华神经医学杂志》2020年第4期337-343,共7页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金面上项目(81774380);福建省科技厅对外合作项目(201710005);福建省卫健委医学创新项目(2017-CX-44);中央引导地方科技发展专项(2018L3009)。

摘　　要：目的通过弥散张量成像(DTI)和磁共振波谱成像(MRS)技术探讨载脂蛋白E基因敲除(ApoE-/-)小鼠短暂性全脑缺血后学习记忆损害的机制。方法10周ApoE-/-小鼠和C57BL/6小鼠按随机数字表法各分为3组:WT假手术组(n=8),WT 7 d组(n=12),WT 30 d组(n=12);ApoE-/-假手术组(n=8),ApoE-/-7 d组(n=12),ApoE-/-30 d组(n=12)。手术组行双侧颈总动脉缺血再灌注损伤,假手术组只剥离血管不结扎。术后第7天和第30天行Morrris水迷宫实验检测小鼠学习记忆能力,采用DTI技术检测小鼠双侧海马区脑组织各向异性分数(FA)值,MRS技术检测小鼠双侧海马区胆碱复合物(Cho)和N-乙酰天门冬氨酸(NAA)的含量。结果(1)水迷宫实验第2~4天,ApoE-/-7 d组小鼠较ApoE-/-假手术组、WT假手术组及WT 7 d组小鼠逃避潜伏期明显延长,差异均有统计学意义(P<0.05)。从第3天开始,ApoE-/-30 d组小鼠较WT 30 d组小鼠逃避潜伏期明显延长,差异有统计学意义(P<0.05)。ApoE-/-7 d组较WT 7 d组穿越平台次数明显减少,第三象限停留时间明显缩短;ApoE-/-30 d组较WT 30 d组穿越平台次数明显减少,第三象限停留时间明显缩短;差异均有统计学意义(P<0.05)。(2)DTI检测结果显示,ApoE-/-7 d组小鼠双侧海马FA值与WT 7 d组小鼠比较差异无统计学意义(P>0.05)。ApoE-/-30 d组小鼠双侧海马FA值均较WT 30 d组小鼠降低,差异有统计学意义(P<0.05)。(3)MRS检测结果显示,ApoE-/-7 d组小鼠海马Cho和NAA相对含量较WT 7 d组小鼠明显降低,ApoE-/-30 d组小鼠海马Cho和NAA相对含量较WT 30 d组小鼠明显降低,差异均有统计学意义(P<0.05)。结论ApoE-/-小鼠在短暂性全脑缺血损伤后存在明显的学习记忆障碍,其机制与海马白质纤维损伤和神经细胞代谢异常密切相关。Objective To investigate the mechanism of learning and memory impairment of apolipoprotein E-/-(ApoE-/-)mice after transient global cerebral ischemia by diffusion tensor imaging(DTI)and magnetic resonance spectroscopy(MRS).Methods Ten-week-old C57BL/6(WT)mice and ApoE-/-mice were randomly divided into WT sham-operated group(n=8),WT 7 d group(n=12)and WT 30 d group(n=12),and ApoE-/-sham-operated(n=8),ApoE-/-7 d group(n=12)and ApoE-/-30 d group(n=12).The mice in the WT 7 d group,WT 30 d group,ApoE-/-7 d group,and ApoE-/-30 d group received bilateral common carotid artery ischemia-reperfusion injury,while mice in the WT sham-operated group and ApoE sham-operated group only stripped the blood vessels without ligation.On the 7th and 30th d of modeling,Morrris water maze test was employed to detect the learning and memory abilities of these mice;DTI was used to detect the fractional anisotropy(FA)values in the bilateral hippocampus of mice,and MRS was used to detect the contents of choline complex(Cho)and N-acetylaspartate(NAA)in the bilateral hippocampus of mice.Results(1)On 2nd,3rd,and 4th d of water maze experiment,the escape latency of mice in ApoE-/-7 d group was significantly prolonged as compared with that in the ApoE-/-sham-operated group and WT 7 d group(P<0.05);since the 3rd d of water maze experiment,the escape latency of mice in ApoE-/-30 d group was significantly prolonged as compared with that in WT 30 d group(P<0.05).The number of times crossing platform in ApoE-/-7 d group was significantly smaller than that in WT 7 d group,and the residence time in the third quadrant was significantly shorter(P<0.05);the number of times crossing platform in ApoE-/-30 d group were significantly smaller as compared with that in the WT 30 d group,and the residence time in the third quadrant was significantly shortened(P<0.05).(2)DTI results showed that there was no significant difference in bilateral hippocampal FA values between ApoE-/-7 d group and WT 7 d group(P>0.05);the bilateral hippocampal FA values of mice in the

关 键 词：认知障碍 弥散张量成像 磁共振波谱成像 APOE-/-小鼠 

分 类 号：R74[医药卫生—神经病学与精神病学] R44[医药卫生—临床医学]