摘要
目的 观察四血管阻断 (4VO)大鼠海马NMDA受体NMDAR的变化规律 ,探讨其在血管性痴呆 (VD)形成中的作用机制。方法 改良的Pulsinelli 4VO法建立大鼠血管性痴呆模型 ;电脑控制的穿梭箱系统和离体海马脑片诱导的CA1区LTP检测大鼠学习记忆 ;原位杂交方法检测大鼠海马NMDAR1mRNA的表达。结果 VD组大鼠的主动回避反应在 2周时较对照组显著下降 (P<0 0 5 ) ,4周和 2月时更加明显 (P <0 0 1) ,海马脑片长时程增强 (LTP)的诱导出现明显障碍 ;VD组 2周时CA1和CA3区NMDAR1mRNA表达较对照组增高 ,DG区无明显改变 ;4周和 2月时海马各区表达均减低。结论 大鼠海马区NMDAR与学习记忆有关 ,在脑缺血的早期表达增高介导了兴奋毒性作用 ;但在缺血后期 ,NMDARmRNA表达减低可能与学习记忆损害有关 ,为进一步进行NMDAR拮抗剂和激动剂治疗VD的研究提供了实验依据。
Objective To establish a reliable vascular dementia(VD) rat model to study the changes of the NMDAR1mRNA expression in rat's Hippocampus,so as to provide the theoretical basis for the mechanism of NMDAR's effect on cognitive impairment of VD rat model Methods The VD rat model was established by four-vessel occlusion(4VO) The changes of memory ability, LTP and the NMDAR1 mRNA expression in the hippocampus were administered by computerized shuttle training case, extracorporeal hippocampal slices method and in situ hybridization Results Compared with the control group,the AAR in the VD model group was less in the 2nd week, the 4th week and the 2nd month( P <0 05) It was more obviously 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 model group at each time point of the 2nd week,the 4th week and the 2nd month Compared with the control group, at the 2nd week the mean optical density (OD) of NMDAR1mRNA expression in pyramidal cell layer of hippocampus in the VD model group was increased in the CA1 and CA3 regions,but no changes were found in DG region; at the 4th week and the 2nd month,it was decreased in each region Conclusions The hippocampal NMDA receptor is related to the cognitive impairment of VD rat model In the early phase of the brain ischemic reperfusion injury,the expression of NMDAR mRNA increase,which mediate the exitotoxicity,but it decrease in the anaphase,which might be correlated to the learning and memory impairment of VD Therefore it supply the foundation to use antagonist or agonist of EAAs receptor in the VD therapy
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2002年第12期1408-1410,共3页
Journal of Third Military Medical University
关键词
血管性痴呆
认知
NMDAR
LTP
vascular dementia
cognition
NMDA receptor
long term potentiation
