Effect Of Donepezil On Synaptophysin And NMDAR-2B Expression And Neurons Apoptosis In Hippocampal CA1 Of Vascular Dementia Rats

Objective: To investigate the mechanism of action of donepezil in vascular dementia by detect the change of N-Methyl-D-aspartate 2B receptor and Synaptophysin expression and neurons apoptosis in hippocampal CA1 of vascular dementia rats.Method: 1. One hundred and eighteen SD rats with normal learning and memory were divided into three groups by random after they were tested by Morris Water Maze: i.e. sham operation group, operation group and donepezil group. There were two subsets in this three gruops, i.e. 1st mouth and 2ed mouth.2. 2 Vessel occlusion were used to establish the vescular dementia models in operation group and donepezil group rats.3. We studied learning and memory function changes, morphology changes under light microscope, the expression of NMDAR-2B and Syp and neuron apoptosis respectively in hippocampal CA1 by using Morris Water Maze, HE staining, immunohistochemistry and TUNEL.4. We compared the changes of ability of learning and memory, morphology , NMDAR-2B, Syp expression and neuron apoptosis in each group in two time points.5. The income data were represented as mean±SD. We arranged the date by the EXCEL database and analysised the date by SPSS13.0 statistics software. We expressed the mean of mV and var as mean±SD. We used the variance analysis of single factor between interclass. Results: 1. The learning and memory ability of donepezil group rats were higher than of operation group rats, and there were significant difference(p<0.01).2. The cellular structure was normal in sham operation groups under light microscopy. However, HE staining of operation groups show ischemic injury, exudation were apparent, then attenuated gradually, the degenetation and detachment of hippocampal CA1 neurons could be seen. The cellular structure were similar to sham operation groups of donepezil groups.3. The expression of NMDAR-2B and Syp was detected to increase at the hippocampal CA1 of sham operation groups and donepezil groups and decrease of operation gruops. The average opitical densities of sham operation groups and donepezil groups were higher than of operation groups, and there were significant difference (p<0.01).4. Positive apoptosis cells were slight in sham operation groups, but apoptosis cell were significantly increased in operation groups. Compared with operation groups, the number of apoptotic cells in donepezil groups greatly declined, and there were significant difference(p<0.01).Conclusion: 1. The reliable vascular dementia rat model could be established by 2 vessel occlusion.2. The expression of NMDAR-2B and Syp was decreased in hippocampal CA1 of vecular dementia rats at both 1st and 2ed mouth, lead to the EAA increase and overloading of Ca2+ and contributed to the apoptosis and necroses of neruons.3. Donepezil could protect neurons and improve the ability of learning and memory by decreased EAA and guarding against overloading of Ca2+, through increase expression of NMDAR-2B and Syp.