双侧颈、椎动脉阻断大鼠血管性痴呆模型的评价

The evaluation of vascular rat model by four-vessel occlusion

目的 对四血管阻断大鼠血管性痴呆模型进行评价 ,为血管性痴呆的基础研究提供合适的动物模型。方法 改良的Pulsinelli’s四血管阻断法建立大鼠血管性痴呆模型 ;血管造影证实双侧椎动脉阻断确切 ;电脑控制的穿梭箱系统和离体海马脑片诱导的CA1区长时程增强检测大鼠学习记忆。结果 血管性痴呆组大鼠椎动脉阻断确切 ,穿梭箱检测AAR在 2周时较对照组显著下降 (P <0 .0 5 ) ,4周和 2个月时更加明显 (P <0 .0 1) ,海马脑片长时程增强的诱导出现明显障碍。结论 四血管阻断法建立的大鼠反复缺血再灌注和慢性低灌流模型可以导致不可逆的学习记忆损害 ,是目前模拟临床血管性痴呆病人发病特点的较理想动物模型。

Objective To establish a reliable vascular dementia(VD) rat model, so as to provide the animal basis for the research of VD.Methods The Wistar rats were randomized into two groups: the control group and the VD group.Each group was observed at 3 time points:the 2nd week,the 4th week and the 2nd month. The VD rat model was established by four vessel occlusion(4VO). The reliability of rat model was verificated by vessel angiography.The changes of memory ability, long term potentiation(LTP) in the hippocampus CA1 zone were administered by computerized shuttle training case, extracorporeal hippocampal slices method.Results In vessel angiography examination, we found the brain blood supply mainly depended on the bilateral common carotid arteries after the occlusion of bilateral common vertebral arteries of the rats.After the occlusion of bilateral common carotid arteries,the consciousness of the rats lost and the righting reflex disappeared.Compared with the control group,the AAR in the VD group was less in the 2nd week, the 4th week and the 2nd month( P <0.05).It was more obvious at the later two time points( P <0.01).In the slices of extracorporeal hippocampal CA1 region,LTP detection showed that its injury had happened clearly in VD group at each time point of the 2nd week,the 4th week and the 2nd month.Conclusion The 4VO is a reliable vascular dementia model,which can lead to irreversible impairment of learning and memory by chronic hypoperfusion and ischemic reperfusion injury, and simulate the character of clinical VD patient.