重复经颅磁刺激预防创伤后应激障碍的实验研究

发布时间：2018-05-10 08:23

本文选题：创伤后应激障碍 + 弱刺激抑制　；参考：《第四军医大学》2012年硕士论文

【摘要】：研究目的：创伤后应激障碍是指异乎寻常的重大灾难性事件导致患者产生一系列的生理心理综合征，其核心症状是闯入性思维。目前临床诊断创伤后应激障碍主要是基于症状学标准，因其症状的出现滞后于应激事件，病程多迁延为慢性，复发率高，有的患者甚至终生不愈，这些因素导致创伤后应激障碍治疗难度较大，面临诸多挑战。如何早期预防创伤后应激障碍的发生，成为临床精神医学研究的重点之一。目前关于创伤后应激障碍的治疗主要包括危机干预和药物治疗，但疗效均不尽如人意。重复经颅磁刺激作为一种新兴，安全，非侵入性物理治疗手段在创伤后应激障碍治疗中已有应用，但现存的临床研究大多将重复经颅磁刺激作为一种治疗手段，如何采用该方法进行早期干预鲜有研究报道。单次延长应激模型是目前较为成熟的创伤后应激障碍动物模型，由于能够有效的模仿创伤后应激障碍患者神经内分泌改变和部分临床症状而被广泛应用。在此基础之上，我们进行改良，保留了模型原有优点并使其更加稳定，已得到国际同行的认可。目前关于该模型行为学评价标准主要采用旷场，高架十字迷宫，水迷宫等检测手段，虽然能够反映模型动物的焦虑水平和认识损害，但不能反映和解释创伤后应激障碍的核心症状—闯入性思维。闯入性思维是指患者不能抑制对创伤性事件的再体验，已有研究表明该症状与负性体验选择滤过功能缺失相关，即存在感觉运动门控通道的损害，并提示其是一种评估创伤后应激障碍的新标准。本研究从制备改良单次延长应激入手，采用重复经颅磁刺激作为早期干预措施，以旷场，高架十字迷宫和惊跳反射的弱刺激抑制检测作为评价标准，在创伤后应激障碍动物模型上探索其预防性作用。研究方法：1.改良单次延长应激对模型大鼠焦虑行为和惊跳反射的弱刺激抑制影响成年雄性sd大鼠48只被随机分为4组，阴性对照组，改良单次延长应激1天组，改良单次延长应激7天组，改良单次延长应激14天组，每组12只大鼠。阴性对照组不接受任何处理，适应性饲养7天后接受旷场，高架十字迷宫，听觉惊跳反射的弱刺激抑制测试；应激组大鼠均适应性饲养7天后接受改良单次延长应激，，三组应激大鼠分别在应激后1天，7天，14天接受旷场，高架十字迷宫，听觉惊跳反射的弱刺激抑制测试。2.重复经颅磁刺激早期干预对应激模型大鼠焦虑行为和惊跳反射的弱刺激抑制影响成年雄性sd大鼠40只被随机分为4组，阴性对照组，改良单次延长应激组，重复经颅磁刺激组，改良单次延长应激+重复经颅磁刺激组，每组10只大鼠。所有大鼠适应性饲养7天。为保证实验均衡性，每组大鼠均接受异氟烷吸入麻醉。除麻醉外，阴性对照组大鼠不给予任何处理饲养7天；改良单次延长应激组大鼠接受改良单次延长应激刺激，之后不受打扰饲养7天；重复经颅磁刺激组大鼠接受重复经颅磁刺激干预7天；改良单次延长应激+重复经颅磁刺激组大鼠接受改良单次延长应激刺激，之后接受重复经颅磁刺激干预7天。处理结束后所有大鼠均接受旷场，高架十字迷宫，听觉惊跳反射的弱刺激抑制测试。研究结果： 1.应激对大鼠焦虑行为和听觉惊跳反射的弱刺激抑制的影响各组大鼠自发活动差异没有统计学意义(P＞0.05)，改良单次延长应激1天组大鼠旷场中央运动路程，中央运动时间，中央运动路程百分比均低于正常对照组大鼠，差异有统计学意义(P＜0.05)，中央运动时间百分比与正常对照大鼠差异没有统计学意义(P＞0.05)，但有下降的趋势；改良单次延长应激7天组大鼠中央运动路程，中央运动时间，中央运动路程百分比和中央运动时间百分比均低于正常对照组大鼠，差异有统计学意义(P＜0.05)；改良单次延长应激14天组大鼠中央运动时间和中央运动时间百分比均低于正常对照组大鼠，差异有统计学意义(P＜0.05)，但中央运动路程和中央运动路程百分比与正常对照相比差异没有统计学意义(P＞0.05)，但有下降的趋势。三组应激大鼠开臂滞留时间和开臂滞留时间百分比以及开臂进入次数百分比均低于阴性对照大鼠(P＜0.05)；而在开臂进入次数绝对值指标中四组大鼠差异没有统计学意义（P＞0.05），但改良单次延长应激三组大鼠进入次数呈下降的趋势。三组应激大鼠听觉惊跳反射的弱刺激抑制均值均低于正常对照组大鼠，差异均有统计学意义(P＜0.05)。 2.重复经颅磁刺激早期干预对应激大鼠焦虑行为和听觉惊跳反射的弱刺激抑制影响各组大鼠自发活动差异没有统计学意义(P＞0.05)，改良单次延长应激组中央运动路程，中央运动时间，中央运动路程百分比，中央运动时间百分比低于其它三组大鼠，差异均有统计学意义(P＜0.05)。改良单次延长应激组大鼠开臂滞留时间和开臂滞留时间百分比低于其余三组大鼠(P＜0.05)，开臂进入次数绝对值和进入次数百分比四组大鼠差异没有统计学意义(P＞0.05)，但改良单次延长应激组呈现下降趋势。改良单次延长应激组大鼠听觉惊跳反射的弱刺激抑制均值低于其余三组大鼠，差异有统计学意义(P＜0.05)。研究结论： 1.改良单次延长应激大鼠在应激后表现出持久的焦虑样行为。听觉惊跳反射的弱刺激抑制损害出现在应激后早期，在应激源去除后损害呈持续性存在。为早期干预提供了理论基础。 2.重复经颅磁刺激早期干预能够逆转应激模型大鼠焦虑行为和听觉惊跳反射的弱刺激抑制的损害。提示应激后重复经颅磁刺激早期干预，可能是预防创伤后应激障碍发生的一种有效保护性措施。
[Abstract]:Purpose of study :

Post - traumatic stress disorder refers to a series of physiological and psychological syndromes caused by an unusually large catastrophic event . The core symptom of the post - traumatic stress disorder is based on the criteria of symptoms .

At present , the treatment of post - traumatic stress disorder mainly includes crisis intervention and drug therapy , but the curative effect is not satisfactory . The repeated use of cranial magnetic stimulation as a new , safe and non - invasive physical therapy has been used in the treatment of post - traumatic stress disorder .

A new model of stress disorder in posttraumatic stress disorder was established , which was used in the animal model of posttraumatic stress disorder .
All the rats were randomly divided into 4 groups , negative control group , modified single extended stress group , repeated transcranial magnetic stimulation group , modified single extended stress + repeated transcranial magnetic stimulation group . All the rats received isoflurane inhalation anesthesia for 7 days .
The modified single - extended stress group rats received improved single - time prolonged stress stimulation , and then the rats were not disturbed for 7 days ;
repeating the repeated cranial magnetic stimulation for 7 days after repeated cranial magnetic stimulation ;
The modified single - extension stress + repetitive transcranial magnetic stimulation group received modified single - time prolonged stress stimulation , followed by repeated cranial magnetic stimulation for 7 days . All the rats received open - field , elevated cross - maze , auditory evoked weak stimulus suppression test after treatment .

Results of the study :

1 . There was no significant difference ( P > 0.05 ) between the effects of stress on the anxiety behavior of rats and the weak stimulus of auditory evoked reflex ( P > 0.05 ) , and the difference was statistically significant ( P < 0.05 ) . The difference between the central exercise time and the normal control rats was not significant ( P > 0.05 ) , but there was a tendency of decline .
Compared with the control group , the difference was statistically significant ( P < 0.05 ) .
Compared with the normal control group , the difference was not significant ( P > 0.05 ) , but there was no significant difference between the central motor distance and the normal control group ( P > 0.05 ) .

The percentage of open arm retention time and open arm retention time of three groups of stress rats were lower than those of negative control rats ( P < 0.05 ) .
However , there was no significant difference between the four groups in the absolute value index ( P > 0.05 ) .

The mean value of the weak stimulus was lower than that of the normal control group , and the difference was statistically significant ( P < 0.05 ) .

2 . Effects of repeated early intervention on anxiety behavior and auditory evoked reflex in stress rats

There was no significant difference in the spontaneous activity of the rats in each group ( P > 0.05 ) , the central movement distance , the central movement time , the central movement distance percentage and the central movement time of the modified single - time prolonged stress group were lower than those of the other three groups ( P < 0.05 ) .

Compared with the other three groups ( P & lt ; 0.05 ) , there was no significant difference in the number of open arms ( P > 0.05 ) .

The difference was statistically significant ( P < 0 . 05 ) .

Conclusions of the study :

1 . The improved single - extension stress rats showed a lasting anxiety - like behavior after stress . The weak stimulus - inhibitory effect of auditory evoked reflex appeared in the early stage after stress , and the lesion appeared durative after the stress source was removed . The theoretical basis was provided for early intervention .

2 . Repeated cranial magnetic stimulation early intervention can reverse the damage of the stress model rats ' anxiety behavior and the weak stimulus suppression of auditory evoked reflex . It is suggested that early intervention after stress can be an effective protective measure to prevent posttraumatic stress disorder .

【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.5

【共引文献】