The Effect Of Simvastatin On Activity Content Of β-secretase And Expression Of β-Amyloid Protein Of The AD Model Rats

Objective: To establish a rat model of Alzheimer's disease, to investigate the functional mechanism and remedy effect of simvastatin on learning and memory,activity content ofβ-secretase and expression ofβ-Amyloid Protein in hippocampal of the AD model rats.Methods:This study choose healthy male Wistar 32 rats of 3-5 months, the rats were randomly divided into four groups: control group, model group and simvastatin high and low dose group. Except the control group was injected 1μL normal saline in the bilateral hippocampal CA1 area, other groups was injected constant volume accumulation Aβ_1-40 to establish AD model rats. Each group was lavaged with regulated dose, a week later, we tested learning and memory ability of the rats by Morris water maze, to compare the results of the group differences. ADministered over four weeks, to decapitate, take out brain, and separate the right hippocampus for measuring activity content ofβ-secretase, The left hippocampus were separated, and the sections were subjected to immunohistochemical methods to measured theβ-Amyloid Protein expression of hippocampus.Results:1,The Morris water maze test manifested: compared with the control group,the escape latency of the model group is longer(P<0.01), the percentage of time of crossing the platform occupying total time is shorter (P<0.01);high and low dose of simvastatin group have shorter the escape latency than the model group (P<0.01),moreover ,there is no significant difference between two groups, and the percentage of time of crossing the platform occupying total time is longer than modle group, which has the obvious difference (P<0.05).2,The result of immunohistochemistry revealed that the grey scale in hippocampus of model group is the lowest, which suggested that the deposition of Aβis the most, and compared with the control group(P<0.01).But the high and low dose of simvastatin group's increased significantly compared with the model group, meaning that the deposition of Aβdecreased (P<0.01), but there is no significant difference between two groups.3,Compared with the control group, the activity content ofβ-secretase increased obviously in the model group,which has the obvious difference (P<0.01). compared with the model group, the activity content ofβ-secretase decreased in the high and low dose of simvastatin group, there is significant difference(P<0.01).The difference between the high and low dose of simvastatin group didn't reach statistically significance.Conclusion: 1,The rat model of AD basically simulated the decreasing of learning and memory of AD and the overexpressed of Aβ.2,Simvastatin improves the learning and memory ability caused by Aβ1-40 of AD rats.3,Simvastatin can reduce AD rats the deposition of Aβ.4,Simvastatin can reduces the activity content ofβ-secretase in the hippocampal tissue.