EGCG对APP/PS1双转基因小鼠神经突触损伤的保护作用

Protective effect of EGCG on neurosynaptic damage in APP/PS1 double transgenic mice

目的:研究表没食子儿茶素没食子酸酯(epi-gallocatechin-3-gallate,EGCG)对APP/PS1双转基因小鼠中神经突触损伤的保护作用及其可能机制。方法:实验采用APP/PS1双转基因小鼠,随机分为模型组(0.1 mL/10 g,生理盐水灌胃)、EGCG组[20 mg/(kg·d),EGCG灌胃],每组10只,另以同窝同性别阴性小鼠10只设立正常组(0.1 m L/10 g,生理盐水灌胃),共3组。Morris水迷宫实验测试各组小鼠逃避潜伏期和跨越平台变化,电镜观察各组小鼠海马神经元损伤情况,免疫组化法检测小鼠海马PSD95、GAP43表达,RT-PCR检测小鼠海马PSD95 mRNA、GAP43 mRNA含量。结果:模型组逃避潜伏期明显延长,海马神经元损伤严重,PSD95表达下降、GAP43表达增高。免疫组化结果表示,EGCG组PSD95平均光密度高于模型组[(0.11±0.03)vs.(0.05±0.02),P=0.001],EGCG组GAP43平均光密度低于模型组[(0.10±0.03)vs.(0.16±0.04),P=0.002]。RT-PCR检测结果再次验证,EGCG组PSD95 mRNA表达高于模型组[(0.82±0.11)vs.(0.50±0.06),P=0.000],EGCG组GAP43 mRNA表达低于模型组[(1.12±0.11)vs.(1.56±0.16),P=0.000]。结论:EGCG对APP/PS1转基因小鼠的空间学习记忆和突触损伤具有明显的改善作用,其机制可能与影响小鼠海马突触结构,提高PSD95表达、下调GAP43表达有关。

Objective:To study the protective effect of EGCG on neurosynaptic damage in APP/PS1 double transgenic mice and its possible mechanism.Methods:APP/PS1 double transgenic mice were randomly divided into two groups:model group(0.1 mL/10 g,normal saline infusion),EGCG group(20 mg/(kg·d),EGCG infusion)Ten negative mice in the same sex were treated with normal group(0.1 mL/10 g,normal saline infusion).Morris water maze was used to test the escape latency and platform-crossing changes of mice in each group.Electron microscopy was used to observe the damage of hippocampal neurons in each group.Immunohistochemical method was used to detect the expression of PSD95 and GAP43 in hippocampus of mice.RT-PCR was used to detect the content of PSD95 mRNA and GAP43 mRNA in hippocampus of mice.Results:The escape latency of the model group was significantly prolonged,the hippocampal neurons were severely damaged,the expression of PSD95 was decreased,and the expression of GAP43 was increased.The results of immunohistochemistry showed that the average optical density of PSD95 in EGCG group was higher than that in model group[(0.11±0.03)vs.(0.05±0.02),P=0.001]and that of GAP43 in EGCG group was lower than that in model group((0.10±0.03)vs.(0.16±0.04),P=0.002)The results of RT-PCR showed that the expression of PSD95 in EGCG group was higher than that in model group((0.82±0.11)vs.(0.50±0.06),P=0.000)The expression of GAP43 in EGCG group was lower than that in model group((1.12±0.11)vs.(1.56±0.16),P=0.000)Conclusion:EGCG can significantly improve the spatial learning,memory and synaptic damage of APP/PS1 transgenic mice.The mechanism may be related to the effect of EGCG on the synaptic structure of hippocampus,the increase of PSD95 expression and the down-regulation of GAP43 expression.