文拉法辛对慢性应激抑郁模型大鼠脑内ERK1、ERK2磷酸化水平及Egr-1表达的影响

Effect of Venlafaxine on the Changes of Cerebral Phosphorylated ERK1,ERK2 and Egr-1 in Rats with Chronic Stress Depression

目的:探讨文拉法辛对慢性应激抑郁模型大鼠不同脑区细胞外信号调节激酶(ERK1/ERK2)含量和活性及即刻早期反应因子(Egr-1)的影响。方法:以旷场试验得分评价大鼠行为,将成年SD大鼠随机分为正常对照组、抑郁模型组、抑郁模型+文拉法辛混悬液低、中、高剂量(15、30、60 mg.kg-1.d-1)灌胃组。用慢性轻度不可预见性应激加分养方法建立抑郁大鼠模型,采用蛋白印迹法检测大鼠前额叶、海马、下丘脑、纹状体磷酸化p-ERK1、p-ERK2和非磷酸化ERK1、ERK2蛋白及Egr-1的表达水平。结果:不同剂量文拉法辛组旷场行为得分较给药前有明显升高(P<0.01),而模型组给药前后无改善(P>0.05);除前额叶部位不同剂量文拉法辛组p-ERK1、p-ERK2表达水平较模型组高外,其余各部位各组p-ERK1、p-ERK2、ERK1、ERK2、Egr-1表达水平比较均无显著性差异(P>0.05)。结论:文拉法辛可能通过上调前额叶部位ERK1、ERK2磷酸化水平,明显改善慢性应激抑郁模型大鼠的抑郁样行为。

OBJECTIVE： To explore the effect of venlafaxine on the content and activity of different cerebral region ERK1/ERK2 and Egr-1 in rats with chronic stress depression.METHODS： The behavior of rats was evaluated by open field test score.The male adult SD rats were randomly divided into normal control group（NC group）,depression model group（DM group） and depression model＋Venlafaxine suspension low-dose,medium-dose and high-dose（15,30,60 mg·kg-1·d-1） groups（LV,MV and HV group）.Chronic mild unpredictable stress score method was used to establish depression rat model.Western blotting was used to determine the expression of phosphorylated p-ERK1 and p-ERK2,phosphorylated ERK1,ERK2 protein and Egr-1 in prefrontal cortex,hippocampus,striatum and hypothalamus of rats.RESULTS： The behavior of open field test in model rats were significantly improved after the treatment of different dose venlafaxine（P0.01）,there was no improvement in DM group before and after treatment（P0.05）;after venlafaxine treatment,the levels of p-ERK1,p-ERK2 in prefrontal cortex in LV,MV and HV groups markedly increased compared with DM group,and there were no significant difference for the level of p-ERK1,p-ERK2,ERK1,ERK2 and Egr-1 in other parts（P0.05）.CONCLUSION： Venlafaxine could improve depressive-behaviors of rats with chronic stress depression,through up-regulating phosphorylation of ERK1,ERK2 signaling pathway in prefrontal cortex.