捕食应激致大鼠持续性情绪唤醒障碍时血浆皮质酮及海马皮质类固醇受体表达变化

目的 探讨严重心理应激所致情感行为异常的相关神经生物学机制.方法 将136只雄性Wistar大鼠随机分为捕食应激组(以下简称应激组)和正常对照组(以下简称对照组),每组68只.以放射免疫分析法检测应激后1 h、1 d、1周,以及1,2,4个月时血浆皮质酮水平,并采用免疫组化和蛋白质免疫印迹法,检测海马糖皮质激素受体(GR)及盐皮质激素受体(MR)表达的变化规律.结果 (1)血浆皮质酮水平:应激后1 h应激组[(44.5±9.3)μg/L]高于对照组[(22.6±4.0)μg/L,P＜0.01],但应激后1 d降至正常水平,而应激后1周至4个月则明显低于对照组[应激组分别为(μg/L)12.4±2.5,9.8±2.1,8.7±2.1,10.1±2.3,对照组分别为(μg/L)20.8±3.9,21.1±4.2,16.6±3.6及20.2±4.0;P＜0.01].(2)海马GR和MR阳性免疫反应信号:应激后1 d免疫组化研究显示,应激大鼠海马及额叶皮层GR均较对照组增强(P＜0.01),其中以海马结构的改变更明显(P＜0.05);而MR则显著降低(P＜0.01).海马免疫印迹检测进一步揭示,应激组海马GR表达于应激后1 d至4个月明显增高(P＜0.05),而MR表达则于应激后1 h至1个月显著低于对照组(P＜0.05).结论 捕食应激后大鼠出现血浆皮质酮双向变化、海马GR和MR失衡以及不同的变化规律,这种严重的心理应激在引发大鼠持续性情绪唤醒障碍中可能有重要作用.

Alterations of plasma corticosterone and hippocampal corticosteroid receptors in rats with the lasting emotionality following predator stress

Objective To explore the neurobiological basis involved in the pathogenesis of the lasting emotionality following severe psychological stress.Methods Altogether 136 male Wistar rats were randomly divided into two groups,and the predator stress group(n=68)was for non-injurious exposure of cats until slightly frightened twitch and nares flaring due to polypnea for 6 min,and normal control group (n=68).The plasma concentrations of corticosterone and expressions of glucocorticoid (GR)and mineralocorticoid receptors (MR) in hippocampus were investigated by radioimmunoassay,immunohistochemistry and the Western blot analyses.Results The plasma corticosterone concentration in stress rats was significantly increased at 1 h after predator stress compared with the controls[(44.5±9.3)vs.(22.6±4.0)μg/L,P<0.01],then declined to the normal level on 1 d after cat exposure.However,the stress rats showed a lasting significant reduction in plasma corticosterone levels from 1 week to 4 months (μg/L)12.4±2.5,9.8±2.1,8.7±2.1 and 10.1±2.3 in stress rats vs.(μg/L)20.8±3.9,21.1±4.2,16.6±3.6 and 20.2±4.0 in controls(P<0.01).The immunohistochemistry analyses revealed that the GR-immunoreactivity in brain tissue of stress rat was significantly increased than controls at 1 d after cat exposure(P<0.01),and even more higher in hippoeampus(P<0.05),while the MR-immunoreactivity was remarkably decreased than the controls(P<0.01).Meanwhile,the Western analyses revealed further that the expression of hippocampal GR in stress rats increased remarkably from 1 d to 4 months after predator stress compared with the controls(P<0.05),whereas that of MR was significantly reduced from 1 h to 1month after predation(P<0.05). Conclusion The biphasic and lasting alterations of plasma corticosterone and the disbalance of hippocampal GR-MR expressions involved in the neuronal hyperexcitability and dysfunction in rat hippocampus might be involved in the long-term emotionality following severe psychological stress.