盐酸多奈哌齐对血管性痴呆小鼠转录因子环磷酸腺苷反应元件结合蛋白表达的影响

目的探讨盐酸多奈哌齐对血管性痴呆(VD)小鼠对海马转录因子环磷酸腺苷反应元件结合蛋白(CREB)表达的调节作用。方法采用双侧颈总动脉反复缺血-再灌注法制备小鼠VD模型。90只雄性昆明小鼠随机分为3组,假手术组(30只)、模型组(30只)及盐酸多奈哌齐治疗组(30只)。在术后第29、30天,经跳台试验和水迷宫试验进行行为学测试,用免疫组织化学和Western blot方法检测各组小鼠海马CREB的表达变化。结果盐酸多奈哌齐治疗组小鼠的学习和记忆成绩明显高于VD模型组小鼠(P<0.05);盐酸多奈哌齐治疗组小鼠海马CA1区CREB蛋白阳性表达的平均吸光度值显著高于VD模型组(P<0.05)。结论盐酸多奈哌齐能够上调VD小鼠CREB的表达。

The effect of donepezil on expression of CREB in hippocampus of mice with vascular dementia

Objective To study the effect of donepezil on the expression change of cAMP response element binding protein(CREB) in hippocampus of mice with vascular dementia(VD).Methods The models of VD mice were established through three times ischemia-reperfusion of bilateral common carotid arteries.Ninety Kunming mice were randomly divided into sham group(n=30),model group(n=30)and treatment group(treated with donepezil,n=30).The behavioral scores were investigated by step-down test and water maze test at day 29 and 30,respectively.The expression of CREB was examined in hippocampus of mice by immunohistochemistry and Western blot methods.Results The grades of learning and memory of mice treated with donepezil is obviously increased than those in VD mice(P<0.05);The expression of CREB in hippocampus of mice treated with donepezil was higher than that in VD mice observed by immunohistochemistry and Western blot methods(P<0.05).Conclusion Donepezil could up-regulate the expression of CREB in hippocampus of mice with vascular dementia.