电休克干预对嗅球切除抑郁模型大鼠海马Glu浓度和Tau蛋白过度磷酸化的影响

摘要

目的 观察不同电量和不同时程电休克干预对嗅球切除抑郁模型大鼠海马Glu浓度和Tau蛋白过度磷酸化的影响.方法 建立大鼠嗅球切除抑郁模型,采用随机单位组3×3析因设计:将每只大鼠视为1个单位,对每个单位给予3个处理因素,即电量因子(3个水平:25、50、75 mA)和时程因子(3个水平:3、6、9次电休克)的所有组合(共9组,n=6).全部电休克处置结束12h内留取海马,高效液相色谱法检测Glu在海马中的含量,Western blot检测p-PHF-1Ser396/404、P-AT8Ser199/202、p-12E8Ser262在海马中的表达.结果 电休克引发海马Glu浓度升高及Tau蛋白磷酸化加剧,且电休克的电流和时程均可影响这一过程,两者的作用是相加的.结论 电休克导致海马Glu浓度升高,从而加剧海马Tau蛋白的磷酸化程度.%Objective To explore the effect of the electroconvulsive shock (ECS) on the glutamate level and the hyperphosphorylation of tau protein in depressed rats. Methods The depression rat models whose olfactory bulbs were removed were established. Using the analysis of variance of factorial design, we set up two intervention factors including electric current (three levels; 25, 50, and 75 mA) and duration (three levels; 3, 6, and 9 times) , which constituted 9 combinations (n =6). Fifty-four adult depression rat models whose olfactory bulbs were removed were randomly divided into nine experimental groups (n =6 in each group). The hippocampus was removed within 12 hours after the ECS finished. The level of glutamate in the hippocampus was detected by high-performance liquid chromatography, and that of Tau protein, which includes p-PHF-1 ser96/404 > p-AT8Serl99/202, and p-12E8See262, in the hippocampus with Western blot analysis. Results The glutamate level and the hyperphosphorylation of tau protein in the hippocampus of depressed rats remarkably increased. The changes of the hyperphosphorylation of tau protein were correlated with the electric current and duration of ECS, and these two factors showed an synergic effect. Conclusion ECS enhances the hyperphosphorylation of tau protein in the hippocampus of depressed rats by up-regulating the glutamate level.