目的 探讨建立创伤后应激障碍(post trauma stress dysfunction,PTSD)大鼠模型的方法,为深入研究创伤后应激障碍的发病机制及药物干预提供科学依据.方法 成年雄性SD大鼠随机分为空白对照组(control组,n=12)和单次延长应激(single prolonged stress,SPS)组(SPS组,n=12),采用单次延长应激的方法建立PTSD大鼠模型.依次给予大鼠高架十字迷宫(elevated plus maze,EPM)、旷场(open-field,OF)、Morris水迷宫(Morris water maze,MWM)实验,在SPS结束后15 d开始EPM和OF实验.在EPM实验中记录大鼠5 min内开臂停留时间、进入开臂的次数;大鼠在OF实验中持续时间为15 min,测定大鼠的活动次数等行为学指标.大鼠在SPS实验后第16 ~ 21天行MWM实验、第16 ~ 20天行定位航行实验,第21天行空间探索实验.经上述实验评定大鼠对环境的恐惧反应、警觉性、焦虑/抑郁行为以及学习记忆能力的变化.结果 高架十字迷宫实验中,SPS组大鼠的开臂进入次数百分比和开臂停留时间百分比比空白对照组明显减少[(23.55±3.79)%与(37.83±4.07)%比较,(11.45±2.77)%与(17.85±3.45)%比较,P〈0.05];旷场实验中SPS组大鼠水平活动距离、中央停留时间比空白对照组明显减少[(4 557.35 mm与8 775.845 mm比较,(22.65±1.54)s与(37.12±4.10)s比较,P〈0.05];Morris水迷宫实验中,SPS组定位航行实验大鼠第1 ~ 5天上台所经过的距离和上台潜伏期逐渐延长,与空白对照组比较差异有统计学意义(P〈0.05);第6天定位航行实验中,SPS组在靶象限花费时间的百分比和穿台次数显著少于空白对照组[(32.15±2.82)%与(51.68±4.38)%比较,(1.15±0.26)次与(2.87±0.35)次,P〈0.05].结论 SPS后,大鼠的空间认知能力下降,焦虑、恐惧情绪增加,探究行为抑制、呆滞.本模型成功诱发了大鼠多种PTSD样精神和行为异常表现,为进一步研究PTSD发病机制及药物干预提供了理想的动?
Objective To establish post trauma stress dysfunction (PTSD) model, provide basis for further research on pathogenesis and pharmacological intervention of PTSD. Methods SD rats were randomly divided into blank control group ( control group, n = 12) and single prolonged stress group (SPS group, n = 12 ). SPS method was adopted to establish rat PTSD model. The elevated plus maze ( EPM), open-field (OF) and Morris water maze (MWM) tests were applied to examine the effects of SPS. For the following 15 days after SPS, EPM and OF tests were done and recorded the percentage of the open-arm staying time, the percentage of counts of the open arm pause and the behavior of the SPS rats within 15 minutes, analyzed the behavioral indexes such as activity times and horizontal motion distance etc. From the 16th day to the 21s' day after SPS, conduct MWM experiment, from 16^th day to 20^th day positioning navigation experiment and the 21^th day space exploration experiment. With above experiments, evaluate rats' fear response to environment, high alertness, anxiety & depression behavior, and learning and memory ability. Results In EPM experiment, compared with control group, there are significant decrease in the percentage of rats' entering open-arm and remaining time in open-arm for SPS group [ ( 23.55 ±3.79 ) % vs. ( 37.83 ± 4.07)%, (11.45±2.77)% vs. (17.85±3.45)%, P〈0.051. In the OF test, compared with control group, there are significant decrease in rats' horizontal motion distance and remaining time in the center for SPS group [ (4 557.35 mm vs. 8 775. 845 mm, (22. 65±1.54) s vs. (37. 12±4. 10) s, P〈0. 051. In the first 5 day positioning navigation experiment, for SPS group, the time of rats' getting on board and remaining on board increased gradually. In the 6th day's positioning navigation experiment, for SPS group, there are obvious increase in target quadrant time and the number of crossing board in comparison with control group [ (32. 15±2. 82