CAJ | 학술논문

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.
목적 탐토엄중심리응격소치정감행위이상적상관신경생물학궤제.방법 장136지웅성Wistar대서수궤분위포식응격조(이하간칭응격조)화정상대조조(이하간칭대조조),매조68지.이방사면역분석법검측응격후1 h、1 d、1주,이급1,2,4개월시혈장피질동수평,병채용면역조화화단백질면역인적법,검측해마당피질격소수체(GR)급염피질격소수체(MR)표체적변화규률.결과 (1)혈장피질동수평:응격후1 h응격조[(44.5±9.3)μg/L]고우대조조[(22.6±4.0)μg/L,P＜0.01],단응격후1 d강지정상수평,이응격후1주지4개월칙명현저우대조조[응격조분별위(μg/L)12.4±2.5,9.8±2.1,8.7±2.1,10.1±2.3,대조조분별위(μg/L)20.8±3.9,21.1±4.2,16.6±3.6급20.2±4.0;P＜0.01].(2)해마GR화MR양성면역반응신호:응격후1 d면역조화연구현시,응격대서해마급액협피층GR균교대조조증강(P＜0.01),기중이해마결구적개변경명현(P＜0.05);이MR칙현저강저(P＜0.01).해마면역인적검측진일보게시,응격조해마GR표체우응격후1 d지4개월명현증고(P＜0.05),이MR표체칙우응격후1 h지1개월현저저우대조조(P＜0.05).결론 포식응격후대서출현혈장피질동쌍향변화、해마GR화MR실형이급불동적변화규률,저충엄중적심리응격재인발대서지속성정서환성장애중가능유중요작용.
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.