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The Study Of Synergetic Effect Of Verapamil Combined Donepezil On Rats Of Alzheimer's Disease

Posted on:2012-11-24Degree:MasterType:Thesis
Country:ChinaCandidate:S ZhengFull Text:PDF
GTID:2154330332996754Subject:Physiology
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Objective: The model of rat of Alzheimer's disease was builded for studying synergetic effect of Verapamil and Donepezil in treating the Alzheimer's disease in rat, to observe the application of the instrument of tri-cylinder intercommunication in the animal ethologic changes. Methods: Male rats,250±30g,were randomly divided equally into the control group, model group, Donepezil group, Verapamil+ Donepezil group (drug combination group) . The luidine blue 5ul was infused in the hippocamp of right for locating the Aβ1-40 by the stereotaxis instrument. Coherent Aβ1-40 (2μg/μl)5μl was infused in the located region for AD model by stereotaxis instrument, the equivalent NS for injection was infused in the same site for control group. All of the rats had been feeding normally for seven days then were gavaged. The rats of Donepezil group were lavaged Donepezil(6.79×10-2mg/ml),the rats of drug combination group were lavaged Verapamil ( 3.825×10-1mg/ml ) and Donepezil (6.79×10-2mg/ml),the rats of control and model groups were lavaged equivalent double distilled water, one time a day for twenty eight days. Then, checkout the ability of each rat of four groups in the behavior of learning and memory with Morris water maze and the instrument of tri-cylinder intercommunication. After the texts, determined each rat's weight, then they were sampled blood through abdominal aortas and determined the indexes of hemorheology respectively, the activity of SOD and AChE and content of MDA in serum, the changes in tissue of the right hippocamps were observed in microscopy. The experimental data was expressed as mean±standard deviation(?x±s), and dealt with the SPSS13.0 software of statistics, P<0.05 for statistical significance. Results: 1. The toluidine blue was distributed in injection site of Aβ1-40 for showing AD successful mode.2. The average running velocity in Morris water maze: Model group(0.82±0.18) compared with the Donepezil group(1.27±0.25),drug combination group(1.29±0.11)and control group ( 1.30±0.33 ) , there were significant differences (P<0.05),there were not significant differences among the Donepezil group,drug combination group and control group.3. Times which the rat crossed the platform: Donepezil group(4.5±2.1)compared with the control group(4.6±2.6), model group(2.7±1.2) and drug combination group(4.7±2.4),there were not significant differences, model group compared with the drug combination group and control group, there were significant differences, there were not significant differences between the drug combination group and control group.4. Times which the rat did not distinguish the correct doors: Model group(2.4±1.5) compared with the Donepezil group(0.9±0.7),drug combination group(0.6±0.7)and control group(0.4±0.5), there were significant differences, there were not significant differences among the Donepezil group, drug combination group and control group.5. The hemorheology: Model group's blood viscosity, plasma viscosity and erythrocyte index of rigidity showed significantly higher than those of control group, Donepezil group and drug combination group, compared drug combination group with Donepezil group, there was statistical significance in cutting down the blood viscosity and erythrocyte index of rigidity, there were no significant differences among the control group, Donepezil group and drug combination group in the most indexes of hemorheology.6. The activity of AChE in serum: Donepezil group(83.99±9.43)compared with the model group (91.04±4.58),control group (77.02±3.54) and drug combination group (80.36±2.57),there were not significant differences, model group compared with the drug combination group and control group, there were significant differences, there were not significant differences between the drug combination group and control group. 7. The activity of SOD and content of MDA in serum: Model group compared with the Donepezil group, drug combination group and control group, there were significant differences, there were not significant differences among the Donepezil group, drug combination group and control group.8. The structure of hippocamp, there were quantities of red senile plaques sedimentated in the hippocamp in the model group, there were few red senile plaques in the same region in the control group, there were few red senile plaques in the same region in the Donepezil group and drug combination group as well, the senile plaques in the drug combination group were less than that in the Donepezil group. Conclusion: 1. AD could be resulted by Aβ1-40 in hippocamp.2. AD rats had hemorheological changes, Verapamil combined Donepezil could cut down the indexes of hemorheology of AD rats and was better than Donepezil.3. The pathologic changes in hippocamp were reduced with Donepezil and Verapamil combined Donepezil for inhibiting the activity of AChE and removing of the free radicle.4.The tri-cylinder intercommunicate could be used for studying of animal behavior.
Keywords/Search Tags:Verapamil, Donepezil, Alzheimer's disease, Instrument of tri-cylinder intercommunication
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