Copy The Alzheimer's Disease Model Of Rat, And Observe The Effects Of Donepezil And Verapamilon In Alzheimer's Disease

Objective: Through copying the Alzheimer′s disease model of rat, to observe the protecting effect and mechanism of Donepezil combine Verapamil in AD rat. And to observe the application of the instrument of tri-cylinder intercommunication in the animal ethologic changes. Methods: A total of forty male Sprague-Dawley rats were divided into four groups, Sham-operated group, Model group, Donepezil (0.525 mg/kg)group, and Donepezil (0.525 mg/kg)+ Verapamil(3 mg/kg) group(Combined treatment group). Aβ1-40 (2μg/μl)5μl was injected in the hippocampus of right for AD model by stereotaxis instrument, and equivalent Saline was injected into Sham-operated group. The rats of Donepezil group were lavaged Donepezil everyday, and Combined treatment group were lavaged Donepezil and Verapamil for twenty eight days after injecting Aβ1-40 seventh days. The rats of Sham-operated and Model group were lavaged di-parboil water everyday for twenty eight days. The Morris water maze and the instrument of tri-cylinder intercommunication were employed to investigate ability of learning and memory in rats. Then all rats were decapitated, and hippocampus and cerebral cortex were dissected respectively to examine the concentrations of AChE, NO and NOS. And using Nissl′s staining to observe the neuronal morphous in CA3 area of the hippocampus. The experimental data was expressed as mean±standard deviation(?x±s), and deal with the SPSS13.0 software of statistics, p<0.05 and p<0.01 for statistical significance. Results: 1 The toluidine blue was distributed in injection site of Aβ1-40 for showing AD successful model. 2 Behavioral detection results: The Morris water maze, compared with Model group, the escape Latency distance of rats in Sham-operated group, Donepezil group and Combined treatment group were significantly decreased(p<0.01); compared with Model group, the swimming distance in the target quadrant of rats in Sham-operated group, Donepezil group and Combined treatment group were increased(p<0.05), and the percentage of distance spent in target quadrant also increased(p<0.05), but Sham-operated group and Combined treatment group significantly increased(p<0.01). the instrument of tri-cylinder intercommuni- cation, compared with Model group, the distance through the area B of rats in Sham-operated group,Donepezil group and Combined treatment group were decreased(p<0.05), but Sham-operated group and Combined treatment group significantly decreased(p<0.01). 3 compared with Model group, Hippocampal ratio of rats in Sham-operated group, Donepezil group and Combined treatment group were decreased(p<0.05), but Sham-operated group and Combined treatment group significantly decreased(p<0.01). 4 compared with Model group, the activity of AChE in Hippocampal of rats in Sham-operated group, Donepezil group and Combined treatment group were decreased(p<0.05), but Sham-operated group and Combined treatment group significantly de- creased(p<0.01). 5 compared with Model group, the content of NO in Hippocampal of rats in Sham-operated group,Donepezil group and Combined treatment group were decreased(p<0.05), but Sham-operated group and Combined treatment group significantly decreased(p<0.01). 6 compared with Model group, the activity of NOS in Cortex of rats in Sham-operated group, Donepezil group and Combined treatment group were decreased (p<0.05). 7 Nissl stain: In Sham-operated group rats, the number of neurons in hippocampus CA3 sector were not loss and spaced neatly; In model group rats, the number of neurons in hippocampus CA3 sector were less and the array of neurons was more irregular than those in Donepezil group and Combined treatment group. Conclusion: 1 The presentation of results of the study that the model was established by Aβ1-40 injected into hippocamal was successful, because the model rats had the changes of praxiology and pathology. 2 The result of Morris water maze test and the instrument of tri-cylinder inter- communication test: the learning and memory of the model rats were decreased obviously, Donepezil and Verapamil can improve the learning and memory of the model rats. 3 Donepezil and Verapamil can dcrease the activity of AChE and the content of NO, dcrease the activity of NOS though reduce the level of Ca2+, improve the cognitive function of the model rats. 4 The tri-cylinder intercommunicate could be used for studying of animal behavior.