本文選題：抑郁癥　切入點(diǎn)：慢性束縛　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：研究背景抑郁癥是一種以顯著、持久的情緒低落為主要臨床特征的常見(jiàn)情感性精神疾病。其發(fā)病率、致死率高。長(zhǎng)期持續(xù)的抑郁癥狀可導(dǎo)致嚴(yán)重的認(rèn)知功能障礙,給患者、家庭以及社會(huì)帶來(lái)了沉重的疾病負(fù)擔(dān)。WHO預(yù)計(jì),2030年抑郁癥將上升為世界第一大負(fù)擔(dān)疾病。盡管大量的科學(xué)研究對(duì)抑郁癥的發(fā)病機(jī)制進(jìn)行了探索,提出來(lái)了各種機(jī)制假說(shuō),但是抑郁癥確切的發(fā)病機(jī)制仍然不清。研究表明慢性應(yīng)激在抑郁癥的發(fā)病中發(fā)揮重要作用,其可導(dǎo)致前額葉(prefrontal cortex,PFC)的結(jié)構(gòu)和功能改變。針對(duì)抑郁癥患者的腦部影像學(xué)研究顯示PFC體積減小及活性降低。由此可知,PFC結(jié)構(gòu)功能改變與抑郁癥的發(fā)生發(fā)展高度相關(guān)。目的本研究采用非靶向氣相色譜-質(zhì)譜聯(lián)用技術(shù)(gas chromatography-mass spectrometry,GC-MS)分析慢性束縛刺激(chronic restraint stress,CRS)抑郁模型大鼠PFC中代謝物質(zhì)改變,從而探索抑郁癥發(fā)病的可能分子機(jī)制。方法1.crs抑郁模型構(gòu)建:領(lǐng)取35只雄性sd(sprague-dawley)大鼠,適應(yīng)環(huán)境一周后,根據(jù)糖水偏好試驗(yàn)和(或)運(yùn)動(dòng)試驗(yàn)的結(jié)果,排除具有異常值的大鼠;剩余的大鼠隨機(jī)分為crs組和正常對(duì)照(non-stressedcontrol,con)組,每天刺激6小時(shí)、連續(xù)刺激21天后對(duì)兩組大鼠進(jìn)行行為學(xué)評(píng)價(jià);最后,根據(jù)糖水偏好試驗(yàn)結(jié)果將crs組分為刺激敏感組和刺激不敏感組,僅刺激敏感組和con組用于后期分析。2.采用非靶向gc-ms代謝組學(xué)方法檢測(cè)兩組大鼠pfc組織代謝譜改變,采用多變量統(tǒng)計(jì)和單變量統(tǒng)計(jì)方法,以及benjamini-hochberg校正后,篩選出crs組和con組之間差異代謝物;采用matlab軟件對(duì)以上差異代謝物進(jìn)行熱圖分析。3.采用ipa軟件對(duì)以上差異代謝物質(zhì)進(jìn)行生物信息學(xué)功能分析,探索參與抑郁癥發(fā)病的代謝通路改變。結(jié)果1.根據(jù)運(yùn)動(dòng)試驗(yàn)結(jié)果值的95%參考區(qū)間和(或)糖水偏好結(jié)果值的95%百分位區(qū)間,排除5只具有異常值的大鼠;剩余的30只大鼠隨機(jī)分為crs組(n=20)和con組(n=10);刺激結(jié)束后,根據(jù)糖水偏好結(jié)果,crs組中8只大鼠被歸為刺激敏感組、12只大鼠為刺激不敏感組;為保持組間平衡,隨機(jī)在con組中挑取8只大鼠;最后,16只大鼠(crs敏感組,n=8;con組,n=8)被用于后期分析。2.與con組相比,crs組大鼠的體重增長(zhǎng)降低(p0.01)、糖水偏好顯著降低(p0.05)、強(qiáng)迫游泳靜止時(shí)間延長(zhǎng)(p0.05),提示CRS組大鼠表現(xiàn)出明顯的抑郁樣行為;在曠野試驗(yàn)和高架十字迷宮試驗(yàn)中,CRS組和CON組之間無(wú)統(tǒng)計(jì)學(xué)差異,提示CRS組大鼠無(wú)焦慮樣行為。3.結(jié)合多變量統(tǒng)計(jì)和單變量統(tǒng)計(jì)方法,以及Benjamini-Hochberg校正后,CRS組和CON組大鼠PFC之間發(fā)現(xiàn)36種差異代謝物。4.生物信息學(xué)功能分析結(jié)果顯示,這36種差異代謝物主要與氨基酸代謝、能量代謝和脂質(zhì)代謝有關(guān)。結(jié)論1.慢性束縛刺激可誘發(fā)大鼠抑郁樣行為,而無(wú)焦慮樣行為。2.采用非靶向GC-MS代謝組學(xué)方法發(fā)現(xiàn)CRS組大鼠的PFC中存在代謝紊亂,這種代謝紊亂主要涉及氨基酸代謝紊亂、能量代謝紊亂和脂質(zhì)代謝紊亂。此結(jié)果為探索抑郁癥的發(fā)病機(jī)制奠定了基礎(chǔ)。
[Abstract]:On the background of depression is a significant and persistent low mood as the main clinical features of common thymogenic mental disease. The incidence rate, high death rate. Long term depression can lead to cognitive dysfunction, serious to patients, families and the society has brought a heavy burden of disease.WHO is expected in 2030 will rise for depression the world's largest burden of disease. Although a large number of scientific research on the pathogenesis of depression are explored, proposed various mechanism hypothesis, but the exact pathogenesis of depression is still unclear. Studies show that chronic stress may play an important role in the pathogenesis of depression, which can lead to the prefrontal cortex (prefrontal cortex, PFC) change the structure and the function of patients with depression. According to brain imaging studies showed decreased PFC activity and volume. Thus, the structure of PFC function and depression. The development of students. The purpose of this study is highly correlated with non target gas chromatography-mass spectrometry (gas chromatography-mass spectrometry GC-MS (chronic) analysis of chronic restraint stress restraint stress, CRS) metabolism of PFC in rat model of depression, and to explore the possible molecular mechanism of the pathogenesis of depression. The construction method of 1.crs model of depression receive: 35 male SD rats (Sprague-Dawley), after a week to adapt to the environment, according to the sucrose preference test and (or) exercise test results, excludinghas abnormal values in rats; the remaining rats were randomly divided into CRS group and normal control group (non-stressedcontrol, con), continuous stimulation for 6 hours every day after 21 days of stimulation evaluation performed on two rats; finally, according to the sucrose preference test results of CRS were divided into sensitive and insensitive stimulation stimulation group, only to stimulate the sensitive group and con group for later analysis by.2. Non targeted metabolomics method for detection of GC-MS PFC in the two groups of rats tissue metabolism profiles, using univariate and multivariate statistical statistical methods, and after benjamini-hochberg correction, were selected between CRS group and con group differences in metabolites; the use of MATLAB software for the above differences into the metabolic thermal analysis of.3. on the metabolism of the above differences bioinformatics analysis using IPA software, explore the metabolic pathway is involved in the onset of depression. Results 1. according to the 95% reference interval and exercise test results (or value) 95% percentile interval sucrose preference value results, 5 were excluded with abnormal values in rats; the remaining 30 rats were randomly divided into CRS group (n=20) and con group (n=10); after stimulation, according to the results of the sucrose preference in the CRS group, 8 rats were classified as sensitive stimulation group, 12 rats for stimulation insensitive group; in order to maintain the balance between groups, in the con group were randomly selected 8 rats; finally, 16 rats (CRS sensitive group, n=8; group con, n=8) to be used in the later analysis of.2. compared with con group, CRS group rats reduced weight gain (P0.01), sucrose preference significantly decreased (P0.05), forced to prolong the swimming immobility time (P0.05), suggesting that the CRS rats showed depression like behaviors were in the wilderness; test and elevated plus maze test, there is no significant difference between CRS group and CON group, CRS group of rats.3. combined with univariate and multivariate statistical methods and statistical anxiety like behavior, after Benjamini-Hochberg correction between CRS group and CON group rat PFC found 36 metabolites.4. bioinformatics analysis showed that the 36 main metabolites and amino acid metabolism, lipid metabolism and energy metabolism. Conclusion 1. chronic restraint stress can induce the depressive like behaviors in rats, without anxiety like behavior of.2. with non targeting GC- MS metabonomics revealed that there was metabolic disorder in the PFC of CRS group. This metabolic disorder mainly involved amino acid metabolism disorder, energy metabolism disorder and lipid metabolism disorder. The results laid the foundation for exploring the pathogenesis of depression.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R749.4;R-332

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相關(guān)期刊論文 前2條

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本文編號(hào)：1730040