【摘要】 目的探讨多奈哌齐(DN)对Aβ所致AD大鼠海马结构损伤的保护作用。方法 36只3月龄Wistar大鼠分为对照组、模型组(侧脑室注射10μg Aβ25-35)、治疗组在模型组基础上腹腔注射多奈哌齐1.5mg/kg/d,持续4w,免疫组化方法观察3组大鼠海马结构3个亚区caspase-3的表达;Western blot方法检测3组大鼠海马结构T-Akt和P-Akt的表达。水迷宫行为学测试3组大鼠的逃避潜伏期。结果模型组与对照组相比大鼠逃避潜伏期明显延长(P<0.01),治疗组较模型组明显缩短(P<0.01)。模型组海马结构3个亚区的caspase-3平均光密度值均较对照组明显增高(P<0.01);而治疗组较模型组减少(P<0.05)。3组之间T-Akt的表达没有差异,但模型组P-Akt的表达量较对照组下调(P<0.05),治疗组P-Akt的表达量较模型组呈上升趋势(P<0.05)。结论多奈哌齐可能是通过上调Akt的磷酸化水平而减少caspase-3的表达,改善大鼠的学习记忆功能。更多还原

【Abstract】 Objective To study the protective effects of Donepezil(DN) on neutron injuries caused by Aβ in rat hippocampal.Methods 36 3-month-old male Wistar rats were divided into 3 groups: control group,model group(10μg Aβ25-35 by intracerebroventricular injection) and treatment group(DN of 1.5mg·kg-1·d-1,ip,for 4 weeks after Aβ treatement).Immunohistochemistry was used to detect the caspase-3 expression in 3 subregions of the hippocampus.Western blotwas used to test the T-Akt and P-Akt levels of the hippocampus.Morris water maze was used to assess the escape latency of all rats.Results Compared with that of the control group,the mean escape latency of the model group was markedly prolonged(P<0.01),while that of the treatment group was markedly shortened(P<0.01).The mean optical density value of caspase-3 of the model group was greatly increased(P<0.01) in all 3 subregions of the hippocampus,while that of the treatment group was decreased(P<0.05).There was no significant difference among the 3 groups in the T-Akt level.But P-Akt was lowered(P<0.05) in the model group,and showed a rising trend(P<0.05) in the treatment group when compared with that of the controls respectively.Conclusion Our results indicate that DN may reduce the caspase-3 expression by increasing the P-Akt level to improve learning and memory injured by Aβ25-35.更多还原