血管性痴呆大鼠海马区长时程增强变化的研究

Changes of long-term potentiation in vascular dementia rat model and its mechanism

目的 观察四血管阻断大鼠海马CA1区长时程增强 (long term potentiation ,LTP)的变化 ,并探讨其可能机制。 方法 改良Pulsinelli’s四血管阻断法建立血管性痴呆大鼠模型 ;采用电脑控制的穿梭箱系统检测大鼠学习记忆 ;离体海马脑片诱导的CA1区LTP检测大鼠学习记忆电生理改变 ;透射电镜观察大鼠海马CA1区的超微结构改变。结果 脑缺血组大鼠AAR在 2w时较对照组显著下降 (P <0 .0 5 ) ,4w和 2m时更加明显 (P <0 .0 1)。对照组海马脑片可明显诱出LTP波形 ,脑缺血组各时相点均几乎诱不出LTP ,条件刺激前后fEPSP斜率变化的百分数与对照组比较差别明显 (P <0 .0 5 ) ;但各时相点间无明显差别。脑缺血组海马CA1区神经元细胞核固缩 ,线粒体肿胀、颗粒减少、电子密度增高 ,轴突脱髓鞘 ,次级溶酶体形成 ,高尔基复合体扩张空泡、神经毡空泡等慢性缺血缺氧改变。结论 海马脑片CA1区LTP检测能够客观地反映大鼠短时记忆损害 。

Objective To observe the changes of neuronal behavior, the hippocampal CA1 zone long term potentiation (LTP) and microstructure in vascular dementia(VD) rat model,to reveal the mechanism of LTP in it.Methods The Wistar rats were randomized into two groups: the control group,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 changes of memory ability, LTP, microstructure were administered by computerized shuttle training case, extracorporeal hippocampal slices method and electron microscopy.Results 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 the VD group at each time point of the 2nd week,the 4th week and the 2nd month. The changes of the ultrastructure were found in the hippocampal neurons of the VD group.The character was that the nuclei pycnosis,the mitochondria swelling,drop decreasing and electron increasing, axis cylinder myelinic layer and demyelination, Golgi complex ectatic vacuole, neuropile vacuole and secondary lysosome occurrenc. No significant change occurred in the structure of synapsis.Conclusions LTP in the extracorporeal hippocampal CA1 region slices is a relieable learning and memory cell model, which can objectively reflect the rat's memory impairment.