慢性应激对大鼠海马神经元PKA和P-CREB蛋白表达的影响及抗抑郁剂的拮抗作用

Effect of chronic stress on PKA and P-CREB expression in hippocampus of rats and the antagonism of antidepressors

目的:探讨慢性轻度不可预见应激对大鼠海马神经元内环磷酸腺苷依赖性蛋白激酶A(cAMP-dependentproteinkinaseA,PKA)和磷酸化的环磷酸腺苷反应元件结合蛋白(phosphorylatedcAMP-responsiveelementbindingprotein,P-CREB)表达的影响以及抗抑郁剂(氟西汀)的拮抗作用。方法:将36只SD雄性大鼠随机均分为正常组、慢性应激模型组、氟西汀治疗组。选用慢性轻度不可预见性应激加孤养造模,应用免疫组织化学以及蛋白质印迹技术研究各组大鼠脑内PKA、磷酸化的CREB(P-CREB)在海马区域的分布以及表达量的差异。结果:免疫组织化学和蛋白免疫印迹结果显示模型组大鼠海马细胞内的PKA和P-CREB蛋白表达量明显低于正常组(P<0.05);氟西汀组大鼠海马细胞内PKA和P-CREB蛋白表达量明显高于模型组(P<0.05)。结论:慢性轻度不可预见性应激可使大鼠海马神经元内的PKA和P-CREB蛋白表达水平下降,氟西汀具有一定的拮抗作用。

Objective To observe the effect of chronic unpredicted sequence of mild stress on the expression of cAMP-dependent protein kinase A （ PKA ） and phosphorylated cAMP-responsive element binding protein （P-CREB） in hippocampus of rats and the antagonism of antidepressors （fluoxetine）. Methods Thirty-six male Sprague Dawley rats were randomly and equally allocated to 3 groups- A normal control group, a model group, and a fluoxetine group. All rats except the control group were singly housed and exposed to an unpredicted sequence of mild stressors. The different distribution and expression of PKA and P-CREB in the hippocampus of rats in different groups were investigated with immuohistochemistry and Westernblot technique. Results The positive PKA and P- CREB cells in the hippocampus of normal controls were the pyramidal cells and the granule cells. The PKA and P-CREB protein expression levels in the hippocampus of model rats were significantly lower than those of the normal controls （P 〈 0. 05 ）. The PKA and P-CREB protein.expression levels in the hippocampus of the fluoxetine group were significantly higher than those of the model group （P 〈 0.05 ）. Conclusion Chronic unpredicted mild stress can affect the PKA and P-CREB expression in hippocampus of rats and fluoxetine has antagonism against it.