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

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 ApoE-/-30 d group were statistically lower than those in WT 30 d group(P<0.05).(3)MRS results showed that the relative contents of hippocampal Cho and NAA in the ApoE-/-7 d group were significantly lower than those in the WT 7 d group,and the relative contents of hippocampal Cho and NAA in the ApoE-/-30 d group were significantly lower than those in the WT 30 d group(P<0.05).Conclusion ApoE-/-mice have poor learning and memory abilities after transient global cerebral ischemic injury,whose mechanism is closely related to the damage of hippocampal white matter fibers and abnormal metabolism of nerve cells.