【摘要】 目的探讨慢性轻度不可预见性应激抑郁模型大鼠脑内ERK1/2含量和活性的变化,为进一步从信号传导的角度阐明抑郁症的分子病理机制提供线索。方法20只SD2~3月龄雄性大鼠,随机分为正常对照组10只、应激抑郁模型组10只,应激抑郁模型组经过21d慢性轻度不可预见性应激,以旷场行为总分评定其应激前后行为学改变。正常对照组和抑郁模型组在应激后即断头处死,采用蛋白印迹技术检测大鼠额叶皮质、海马、下丘脑、纹状体磷酸化ERK1/2(p-ERK1/2)和非磷酸化ERK1/2的表达。结果经过21d的慢性应激,应激大鼠旷场行为总分较应激前显著减少(P<0.001)。应激后抑郁模型组额叶部位p-ERK1、p-ERK2含量较正常对照组低,差异有显著性(P<0.001),ERK1/2的表达两组间比较差异无显著性(P>0.05);海马部位p-ERK1、p-ERK2含量也较正常对照组低,但差异无显著性,海马部位ERK1/2的表达两组间比较差异无显著性(P>0.05);纹状体和下丘脑部位p-ERK1/2、ERK1/2含量在应激前后均无明显变化。结论应激大鼠额叶部位p-ERK1/2含量的降低提示ERK信号传导通路的下调可能参与了应激所致抑郁的机制。更多还原

【Abstract】 ObjectiveTo observe the changes of brain ERK1/2 in rats treated with chronic stress so as to further explore the mechanisms of stress damage from view of intracellular signaling transduction.MethodsTwenty adult male SD rats were divided into normal control group(M) and stress group(CA),rats of stress group were exposed to unpredicted mild stressors for 21 consecutive days. An open field test was repeated three times to evaluate the depressive-behavior during the experiment. Rat of M group and CA group were sacrificed by decapitation after 21 day stress, Western blot was used to quantificationally determine the levels of p-ERK1/2 ,ERK1/2 in hippocampus , prefrontal cortex, hypothalamus and striatum.ResultsThe results showed that the total scores of open field tests in stress group was significantly reduced after 21 days stress compared with control group(P<0.001).After stress, the levels of p-ERK1/2 in prefrontal cortex in M group were lower than that in CA group (P<(0.001)).In other examined regions,the levels of p-ERK1/2 and ERK1/2 were unchanged. ConclusionSignificant decrease of p-ERK1/2 levels in prefrontal cortex after 21 days stresses suggested that down regulation of ERK signaling pathway may be involved in the mechanisms of stress damage.更多还原