神经节苷脂对APP/PSI双转基因AD小鼠海马caspase-3和iNOS表达的影响

The effect of monosialoganglioside on expressions of caspase-3 and iNOS in hippocampus of APP/PS1 double transgenic mice of Alzheimer disease

目的本实验利用APP/PS1双转基因阿尔茨海默病(AIzheimer disease,AD)小鼠模型,观察神经节苷脂对AD小鼠学习记忆能力及海马caspase-3与诱导型一氧化氮合酶(iNOS)表达的影响。方法 APP/PS1双转基因模型小鼠20只,随机分为AD模型组(10)和神经节苷脂(GM1)组(10),再取同窝阴性小鼠10只,作为对照组。经跳台试验和水迷宫试验进行行为学测试,用免疫组化方法Western blot方法检测各组小鼠海马caspase-3与iNOS的表达变化。结果 AD模型组小鼠的学习和记忆成绩明显低于对照组(P<0.05),而GM1组小鼠明显高于AD模型组(P<0.05)。AD模型组小鼠海马caspase-3与iNOS蛋白阳性表达的平均光密度值显著高于GM1组小鼠和对照组小鼠(P<0.05)。结论下调AD小鼠海马区caspase-3与iNOS的表达可能是GM1改善AD小鼠学习和记忆功能的机制之一。

Objective To study the effect of monosialoganglioside（GM1） on leaming and memory and the expression level of cysteinyl aspirate specific-proteinase 3（easpase-3） and iNOS in hippocampus of APP/PS1 double transgenie mice of Alzheimer disease（AD）. Methods 20 APP/PS1 double transgenic mice were randomly divided into AD model group（10）, monosialoganglioside（GM1） treatment group（10） and control group（lO）. The behavioral scores were investigated by step-down test and water maze test. The expressions of easpase-3 and iNOS were examined by immunohistochemistry and Western blot. Results Compared with AD group, the grades of learning and memory of mice in monosialoganglioside treatment group or control group were obviously increased （ P〈0.05 ） , The mean optical density（MOD） values of easpase-3 and iNOS positive expression in hippocampus were higher in AD model group than in monosialoganglioside treatment group or control groups. Conclusion The improvement of learning and memory abilities in AD mice by GM1 might be related to the down-regulation of caspase-3 and iNOS expressions in hippocampus.