本文選題：創(chuàng)傷后應(yīng)激障礙 + 弱刺激抑制　； 參考：《第四軍醫(yī)大學(xué)》2012年碩士論文

【摘要】：研究目的： 創(chuàng)傷后應(yīng)激障礙是指異乎尋常的重大災(zāi)難性事件導(dǎo)致患者產(chǎn)生一系列的生理心理綜合征，其核心癥狀是闖入性思維。目前臨床診斷創(chuàng)傷后應(yīng)激障礙主要是基于癥狀學(xué)標(biāo)準(zhǔn)，因其癥狀的出現(xiàn)滯后于應(yīng)激事件，病程多遷延為慢性，復(fù)發(fā)率高，有的患者甚至終生不愈，這些因素導(dǎo)致創(chuàng)傷后應(yīng)激障礙治療難度較大，面臨諸多挑戰(zhàn)。如何早期預(yù)防創(chuàng)傷后應(yīng)激障礙的發(fā)生，成為臨床精神醫(yī)學(xué)研究的重點(diǎn)之一。 目前關(guān)于創(chuàng)傷后應(yīng)激障礙的治療主要包括危機(jī)干預(yù)和藥物治療，但療效均不盡如人意。重復(fù)經(jīng)顱磁刺激作為一種新興，安全，非侵入性物理治療手段在創(chuàng)傷后應(yīng)激障礙治療中已有應(yīng)用，但現(xiàn)存的臨床研究大多將重復(fù)經(jīng)顱磁刺激作為一種治療手段，如何采用該方法進(jìn)行早期干預(yù)鮮有研究報(bào)道。 單次延長(zhǎng)應(yīng)激模型是目前較為成熟的創(chuàng)傷后應(yīng)激障礙動(dòng)物模型，由于能夠有效的模仿創(chuàng)傷后應(yīng)激障礙患者神經(jīng)內(nèi)分泌改變和部分臨床癥狀而被廣泛應(yīng)用。在此基礎(chǔ)之上，我們進(jìn)行改良，保留了模型原有優(yōu)點(diǎn)并使其更加穩(wěn)定，已得到國(guó)際同行的認(rèn)可。目前關(guān)于該模型行為學(xué)評(píng)價(jià)標(biāo)準(zhǔn)主要采用曠場(chǎng)，高架十字迷宮，水迷宮等檢測(cè)手段，雖然能夠反映模型動(dòng)物的焦慮水平和認(rèn)識(shí)損害，但不能反映和解釋創(chuàng)傷后應(yīng)激障礙的核心癥狀—闖入性思維。闖入性思維是指患者不能抑制對(duì)創(chuàng)傷性事件的再體驗(yàn)，已有研究表明該癥狀與負(fù)性體驗(yàn)選擇濾過(guò)功能缺失相關(guān)，即存在感覺(jué)運(yùn)動(dòng)門(mén)控通道的損害，并提示其是一種評(píng)估創(chuàng)傷后應(yīng)激障礙的新標(biāo)準(zhǔn)。本研究從制備改良單次延長(zhǎng)應(yīng)激入手，采用重復(fù)經(jīng)顱磁刺激作為早期干預(yù)措施，以曠場(chǎng)，高架十字迷宮和驚跳反射的弱刺激抑制檢測(cè)作為評(píng)價(jià)標(biāo)準(zhǔn)，在創(chuàng)傷后應(yīng)激障礙動(dòng)物模型上探索其預(yù)防性作用。研究方法：1.改良單次延長(zhǎng)應(yīng)激對(duì)模型大鼠焦慮行為和驚跳反射的弱刺激抑制影響成年雄性sd大鼠48只被隨機(jī)分為4組，陰性對(duì)照組，改良單次延長(zhǎng)應(yīng)激1天組，改良單次延長(zhǎng)應(yīng)激7天組，改良單次延長(zhǎng)應(yīng)激14天組，每組12只大鼠。陰性對(duì)照組不接受任何處理，適應(yīng)性飼養(yǎng)7天后接受曠場(chǎng)，高架十字迷宮，聽(tīng)覺(jué)驚跳反射的弱刺激抑制測(cè)試；應(yīng)激組大鼠均適應(yīng)性飼養(yǎng)7天后接受改良單次延長(zhǎng)應(yīng)激，，三組應(yīng)激大鼠分別在應(yīng)激后1天，7天，14天接受曠場(chǎng)，高架十字迷宮，聽(tīng)覺(jué)驚跳反射的弱刺激抑制測(cè)試。2.重復(fù)經(jīng)顱磁刺激早期干預(yù)對(duì)應(yīng)激模型大鼠焦慮行為和驚跳反射的弱刺激抑制影響成年雄性sd大鼠40只被隨機(jī)分為4組，陰性對(duì)照組，改良單次延長(zhǎng)應(yīng)激組，重復(fù)經(jīng)顱磁刺激組，改良單次延長(zhǎng)應(yīng)激+重復(fù)經(jīng)顱磁刺激組，每組10只大鼠。所有大鼠適應(yīng)性飼養(yǎng)7天。為保證實(shí)驗(yàn)均衡性，每組大鼠均接受異氟烷吸入麻醉。除麻醉外，陰性對(duì)照組大鼠不給予任何處理飼養(yǎng)7天；改良單次延長(zhǎng)應(yīng)激組大鼠接受改良單次延長(zhǎng)應(yīng)激刺激，之后不受打擾飼養(yǎng)7天；重復(fù)經(jīng)顱磁刺激組大鼠接受重復(fù)經(jīng)顱磁刺激干預(yù)7天；改良單次延長(zhǎng)應(yīng)激+重復(fù)經(jīng)顱磁刺激組大鼠接受改良單次延長(zhǎng)應(yīng)激刺激，之后接受重復(fù)經(jīng)顱磁刺激干預(yù)7天。處理結(jié)束后所有大鼠均接受曠場(chǎng)，高架十字迷宮，聽(tīng)覺(jué)驚跳反射的弱刺激抑制測(cè)試。 研究結(jié)果： 1.應(yīng)激對(duì)大鼠焦慮行為和聽(tīng)覺(jué)驚跳反射的弱刺激抑制的影響各組大鼠自發(fā)活動(dòng)差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P＞0.05)，改良單次延長(zhǎng)應(yīng)激1天組大鼠曠場(chǎng)中央運(yùn)動(dòng)路程，中央運(yùn)動(dòng)時(shí)間，中央運(yùn)動(dòng)路程百分比均低于正常對(duì)照組大鼠，差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)，中央運(yùn)動(dòng)時(shí)間百分比與正常對(duì)照大鼠差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P＞0.05)，但有下降的趨勢(shì)；改良單次延長(zhǎng)應(yīng)激7天組大鼠中央運(yùn)動(dòng)路程，中央運(yùn)動(dòng)時(shí)間，中央運(yùn)動(dòng)路程百分比和中央運(yùn)動(dòng)時(shí)間百分比均低于正常對(duì)照組大鼠，差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)；改良單次延長(zhǎng)應(yīng)激14天組大鼠中央運(yùn)動(dòng)時(shí)間和中央運(yùn)動(dòng)時(shí)間百分比均低于正常對(duì)照組大鼠，差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)，但中央運(yùn)動(dòng)路程和中央運(yùn)動(dòng)路程百分比與正常對(duì)照相比差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P＞0.05)，但有下降的趨勢(shì)。 三組應(yīng)激大鼠開(kāi)臂滯留時(shí)間和開(kāi)臂滯留時(shí)間百分比以及開(kāi)臂進(jìn)入次數(shù)百分比均低于陰性對(duì)照大鼠(P＜0.05)；而在開(kāi)臂進(jìn)入次數(shù)絕對(duì)值指標(biāo)中四組大鼠差異沒(méi)有統(tǒng)計(jì)學(xué)意義（P＞0.05），但改良單次延長(zhǎng)應(yīng)激三組大鼠進(jìn)入次數(shù)呈下降的趨勢(shì)。 三組應(yīng)激大鼠聽(tīng)覺(jué)驚跳反射的弱刺激抑制均值均低于正常對(duì)照組大鼠，差異均有統(tǒng)計(jì)學(xué)意義(P＜0.05)。 2.重復(fù)經(jīng)顱磁刺激早期干預(yù)對(duì)應(yīng)激大鼠焦慮行為和聽(tīng)覺(jué)驚跳反射的弱刺激抑制影響 各組大鼠自發(fā)活動(dòng)差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P＞0.05)，改良單次延長(zhǎng)應(yīng)激組中央運(yùn)動(dòng)路程，中央運(yùn)動(dòng)時(shí)間，中央運(yùn)動(dòng)路程百分比，中央運(yùn)動(dòng)時(shí)間百分比低于其它三組大鼠，差異均有統(tǒng)計(jì)學(xué)意義(P＜0.05)。 改良單次延長(zhǎng)應(yīng)激組大鼠開(kāi)臂滯留時(shí)間和開(kāi)臂滯留時(shí)間百分比低于其余三組大鼠(P＜0.05)，開(kāi)臂進(jìn)入次數(shù)絕對(duì)值和進(jìn)入次數(shù)百分比四組大鼠差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P＞0.05)，但改良單次延長(zhǎng)應(yīng)激組呈現(xiàn)下降趨勢(shì)。 改良單次延長(zhǎng)應(yīng)激組大鼠聽(tīng)覺(jué)驚跳反射的弱刺激抑制均值低于其余三組大鼠，差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)。 研究結(jié)論： 1.改良單次延長(zhǎng)應(yīng)激大鼠在應(yīng)激后表現(xiàn)出持久的焦慮樣行為。聽(tīng)覺(jué)驚跳反射的弱刺激抑制損害出現(xiàn)在應(yīng)激后早期，在應(yīng)激源去除后損害呈持續(xù)性存在。為早期干預(yù)提供了理論基礎(chǔ)。 2.重復(fù)經(jīng)顱磁刺激早期干預(yù)能夠逆轉(zhuǎn)應(yīng)激模型大鼠焦慮行為和聽(tīng)覺(jué)驚跳反射的弱刺激抑制的損害。提示應(yīng)激后重復(fù)經(jīng)顱磁刺激早期干預(yù)，可能是預(yù)防創(chuàng)傷后應(yīng)激障礙發(fā)生的一種有效保護(hù)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 .

【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R749.5

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