阿尔茨海默病大鼠海马细胞外调节蛋白激酶的变化

Changes of Extracellular Regulated Protein Kinase in Rats with Alzheimer＇s Disease

目的探讨细胞外调节蛋白激酶（extracellular regulated protein kinase，ERK）与阿尔茨海默病（Alzheimer’Sdisease，AD）发病机制的关系。方法建立穹窿海马伞切断AD大鼠模型．应用Y型迷宫对大鼠进行行为学测试，分别用同位素方法和蛋白质印迹检测了ERK的水平、并用RT-PCR方法检测了ERK2 mRNA的表达。结果Y型迷宫测试发现穹窿海马伞切断AD大鼠学习和记忆的获得和再现均受损；同位素方法检测穹窿海马伞切断大鼠海马ERK的活性，手术组手术侧为（13．46士3．23）pmol·mg^-1·mm^-1，明显高于正常对照组（10．80±1．50）pmol·mg^-1·min^-1、假手术组（10．74土1．62）pmol·mg-^-1·min^-1和手术组非手术侧（10．79±2．23）pmol·mg^-l·min^-1；蛋白质印迹分析显示手术组条带深于正常对照组；RT-PCR显示ERK2 mRNA表达手术组条带亮于正常对照组。结论穹窿海马伞切断AD大鼠海马ERK升高，ERK信号转导途径在AD发病早期起作用。

Objective To study the relationship of extracellular regulated protein kinase（ERK） and mechanism of Alzheimer＇ s disease（AD）. Methods Rat model of AD which was made by transection of rat fimbria-fornix.Learning and memory of rats was tested by Y-type maze.The activity of ERK was determined by using isotope and western blot,and the ERK2 mRNA expression was determined by RT-PCR. Results By using Y-type maze,there are no difference between pseudo-operation group and normal control in learning and memory, learning and memory in operated rats decreased.By using isotope tested activity of ERK in operating side of operated group was （13.46 ± 3.23）pmol.mg^-l·min^-1,which was significantly higher than （10.80±1.50）pmol· mg^-1.min^-1 of normal group,（10.74± 1.62）pmo^-1·mg^-1·min·^-1 of pseudo-operated group and （10.79 ± 2.23）pmo^-l·mg·^-1·min^-1 in unoperating side of operated group;By using Western blot method,level of ERK in operated group was higher than that of normal group;By using RT-PCR, ERK2 mRNA expression in operated group was higher than that of normal group. Conclusion The level of ERK increased in hippocampus of rat model of AD,which showed changes of signal transduction route in the early phase.