石杉碱甲对血管性痴呆小鼠海马NMDA受体及mRNA表达的影响

目的:观测石杉碱甲对血管性痴呆小鼠海马神经元N-甲基D-天门冬氨酸(NMDA)受体免疫组化和原位杂交变化的影响,探讨石杉碱甲干预作用的机制.方法:双侧颈总动脉线结,反复缺血-再灌注法制备模型,药物组用石杉碱甲溶液灌胃,跳台试验和水迷宫试验观测其行为学改变,采用免疫组化和原位杂交技术观测小鼠海马神经元NMDA受体及其mRNA的表达变化.结果:在跳台试验中,模型组小鼠学习阶段的反应时间延长、错误次数增加,记忆阶段的潜伏时间缩短、错误次数增加;水迷宫试验中,其学习阶段的游全程时间延长和错误次数增加,记忆阶段的游全程时间延长和错误次数增加(与假手术组相比,P＜0.01).石杉碱甲明显改善了模型小鼠上述学习、记忆成绩(P＜0.01).同时,药物组海马的NMDA受体及其mRNA表达也较模型组的表达明显增高(P＜0.01),且海马两者的表达在药物组与假手术组间差异无显著性.结论:石杉碱甲改善血管性痴呆小鼠学习、记忆成绩与其恢复海马低水平的NMDA受体及其mRNA有关.

The effect of huperzine A on N-methyl-D-aspartate receptor in neuron of hippocampus in mice with vascular dementia by immunohistochemistry and in situ hybridization

OBJECTIVE To observe the effect of huperzine A on N-methyl-D-aspartate receptor and its mRNA in neuron of hippocampus in mice with vascular dementia. METHODS The mice were subjected for reperfusion repeatedly on bilateral common carotid arteries by knots to establish the VD models. The behavioral abnormalities were investigated by step-down test and water maze test. Huperzine A was given to the mice in medication group, N-methyl-D-aspartate receptor and its messenger ribonucleic acid(mRNA) in neuron of hippocampus were observed by immunohistochemistry and in situ hybridization technique respectively. RESULTS In step-down test, the ability to learning and memory in model group decreased evidently that was reflected by the prolongation of response period and increase of the error times during the learning phase, and by decrease of latent period,and increase of the error times during the memory phase. In water maze test, the reduced notably grades of learning and memory in model group were shown as the prolongation of the whole course time of swimming and increase of the error times during both learning phase and memory phase(vs. sham group, P<(0.01) respectively). whereas, the grades in drug group improved apparently, compared with model group (P<(0.01)). Similarly, the expression of N-methyl-D-aspartate receptor and the mRNA in neuron of hippocampus were ameliorated by Huperzine A(P<(0.01)), and no difference was discovered between drug group and sham group.CONCLUSION Huperzine A improves dysfunction of learning and memory in VD, suggests that huperzine A restored expression of N-methyl-D-aspartate receptor and its mRNA.