创伤后应激障碍样行为异常大鼠海马糖皮质激素与盐皮质激素受体表达研究

Expression of glucocorticoid receptor and mineralocorticoid receptor in hippocampi of rat with posttraumatic stress disorder-like behavior

目的 在建立海马惊厥阈下电刺激创伤后应激障碍 (PTSD)动物模型基础上 ,进一步探讨脑组织糖皮质激素受体 (GR)与盐皮质激素受体 (MR)变化规律。 方法 采用频率 2 5Hz、波宽 1ms、串长 10s、串隔 7min、强度 10 0 μA的恒流、单脉冲电流 ,反复刺激大鼠海马 ,并通过旷场行为及拒俘反应性检查观测大鼠情感行为改变 ;利用免疫印迹法检测脑组织GR与MR表达。 结果 成功诱发了实验大鼠较长时程的活动习性改变 ,警觉水平增高 ,惊恐行为 ,环境适应能力下降 ,躲藏逃避反应等PTSD样行为异常表现。免疫印迹检测显示 ,电刺激停止后 2d～ 1周 ,阈下刺激组大鼠海马GR表达明显增高 ;电刺激停止后 1dMR表达增高 ,2～ 3d则明显降低 ;而额叶皮层二者表达无明显改变。 结论 海马CA1区惊厥阈下电刺激可基本模拟PTSD多种临床表现 。

Objective To observe the expressions of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in brain tissues following establishment of the animal model of posttraumatic stress disorder (PTSD) by subconvulsive electrical stimulation to rat's hippocampus. Methods The hippocampus of Wistar rat was repeatedly stimulated by constant pulsating current with intratrain frequency of 25 Hz, pulsating duration of 1 ms, train duration of 10 seconds, interstimulus interval of 7 minutes and intensity of 100 μA. The emotional behavior of experimental rat was tested by the activity in an unfamiliar open field and the resistance to capture from the open field. The expressions of GR and MR in hippocampi and frontal cortex were detected by Western blotting. Results The stimulated rats tested 1 month after the last stimulation displayed significant abnormalities of PTSD like emotional behavior such as increased anxiety, enhanced startle and delayed habituation, increased resistance to capture and so forth. The Western blot analysis demonstrated that the GR expression in the hippocampi of stimulated rats increased significantly from 2 days to 1 week after stimulation. And the MR expression in the hippocampi increased at day 2, and then decreased markedly 2 3 days after the last stimulation. While the expressions of both receptors in frontal cortex showed no significant changes. Conclusions The animal model of subconvulsive stimulation to rat hippocampus can basically simulate most characteristics of PTSD. The continual high expression of GR expression and the low expression of MR in the hippocampi may play an important role in the neuropsychological sequelae of PTSD.