本文選題：重型抑郁　切入點(diǎn)：雌二醇　出處：《重慶醫(yī)科大學(xué)》2016年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：研究背景重型抑郁(MDD)是普遍多發(fā)的一種精神系統(tǒng)疾病,成人患病率據(jù)估計(jì)在5%-13%,尤其特殊的是男女之間存在著很大的患病率差異,女性患病率大約是男性的1.5-3倍。由于復(fù)雜的生理病理學(xué)因素,目前這種巨大的患病率性別差異仍未得到很好的闡釋。但是可以肯定的是性激素在其中發(fā)揮了重要作用,有關(guān)性激素方面的研究有可能為情感障礙類(lèi)疾病在男女患病率差異上提供一個(gè)突破口。雌二醇(E2)是雌激素中主要的生物活性成分,在體內(nèi)主要以三種形式存在:2-3%呈游離狀態(tài);40-60%與白蛋白結(jié)和,這兩種形式是雌激素在體內(nèi)能夠發(fā)揮生物學(xué)活性的形式。40-60%與性激素結(jié)合球蛋白(SHBG)相結(jié)合,這種形式是不能發(fā)揮生物學(xué)作用的。大量的研究表明雌二醇在情感障礙類(lèi)疾病中發(fā)揮了重要作用,所以檢測(cè)重型抑郁女性患者血清雌激素水平,特別是具有生物活性的雌二醇水平是十分有意義的,而且可以進(jìn)一步了解雌激素水平的變化對(duì)神經(jīng)遞質(zhì)相關(guān)代謝物的影響。目的通過(guò)檢測(cè)女性重型抑郁病人血清雌二醇和性激素結(jié)合球蛋白(SHBG)水平,了解具有生物活性的雌二醇水平與臨床癥狀間的聯(lián)系,進(jìn)一步結(jié)合卵巢切除動(dòng)物模型來(lái)探討雌激素在重型抑郁發(fā)病中對(duì)各種神經(jīng)遞質(zhì)相關(guān)代謝物的影響。方法本實(shí)驗(yàn)總共分為3個(gè)部分1.重型抑郁女性患者和健康對(duì)照女性血清雌二醇和性激素結(jié)合球蛋白(SHBG)水平的檢測(cè),運(yùn)用化學(xué)發(fā)光微粒子免疫檢測(cè)法,購(gòu)買(mǎi)雌二醇和性激素結(jié)合球蛋白標(biāo)準(zhǔn)品及測(cè)定試劑盒,運(yùn)用全自動(dòng)生化免疫分析儀進(jìn)行實(shí)驗(yàn)操作。2.構(gòu)建卵巢切除小鼠模型及其質(zhì)量評(píng)價(jià),包括卵巢切除后小鼠血清雌二醇水平的檢測(cè),糖水偏好和體重測(cè)量,曠場(chǎng)實(shí)驗(yàn)和強(qiáng)迫游泳實(shí)驗(yàn)。3.卵巢切除小鼠海馬和前額葉神經(jīng)遞質(zhì)相關(guān)代謝物的檢測(cè)。主要進(jìn)行了色氨酸通路,gaba通路和兒茶酚胺通路相關(guān)神經(jīng)遞質(zhì)代謝物的檢測(cè)。結(jié)果1.重型抑郁女性患者血清雌二醇水平較健康對(duì)照女性明顯降低,p0.01;性激素結(jié)合球蛋白水平與健康對(duì)照女性沒(méi)有明顯改變。2.卵巢切除動(dòng)物模型構(gòu)建,卵巢切除后小鼠血清雌二醇水平較正常對(duì)照小鼠明顯降低,p0.01。進(jìn)一步檢測(cè)模型動(dòng)物的行為學(xué)發(fā)現(xiàn)卵巢切除后小鼠較正常對(duì)照組小鼠糖水偏好降低,p0.05;體重明顯增加,p0.05。曠場(chǎng)實(shí)驗(yàn)中,卵巢切除后小鼠較正常對(duì)照小鼠水平移動(dòng)得分和垂直運(yùn)動(dòng)得分均沒(méi)有明顯改變。在強(qiáng)迫游泳實(shí)驗(yàn)中發(fā)現(xiàn)卵巢切除后小鼠較正常對(duì)照小鼠不動(dòng)總時(shí)間和不動(dòng)時(shí)間%均明顯增加,p0.05。3.在卵巢切除后小鼠色氨酸通路中的相關(guān)神經(jīng)遞質(zhì)代謝物水平較正常對(duì)照小鼠多數(shù)發(fā)生了較為明顯的下降。如5-ht在海馬和前額葉內(nèi)均發(fā)生了較為明顯的下降,p0.05;n-乙酰五羥色胺(n-as)水平在前額葉內(nèi)發(fā)生了明顯下降,p0.05。另外可以明顯的發(fā)現(xiàn)在海馬內(nèi)犬尿素(kyn)和犬尿胺酸(kya)水平均明顯升高,p0.05。在γ-氨基丁酸(gaba)通路中,可以發(fā)現(xiàn)卵巢切除后小鼠較正常組小鼠前額葉和海馬內(nèi)琥珀酸(sa)水平明顯降低,p0.05;在前額葉內(nèi)谷胱甘肽(gsh)水平較正常組明顯降低,p0.05。在兒茶酚胺通路中,卵巢切除小鼠較正常對(duì)照組小鼠海馬和前額葉內(nèi)神經(jīng)遞質(zhì)相關(guān)代謝物并未發(fā)生較為明顯的改變。結(jié)論1.重型抑郁女性患者血清雌二醇水平明顯降低,SHBG水平并未明顯改變,因此在重型抑郁女性患者體內(nèi)具有生物學(xué)活性的雌二醇水平明顯降低,揭示了在重型抑郁女性患者體內(nèi)雌二醇水平的變化參與了抑郁癥的發(fā)生發(fā)展。2.卵巢切除后,雌激素水平降低的條件下,卵巢切除后的小鼠表現(xiàn)出了較為明顯的抑郁樣行為。比如小鼠糖水偏好程度明顯降低,體重明顯增加,強(qiáng)迫游泳實(shí)驗(yàn)中不動(dòng)時(shí)間明顯增加。3.在雌激素減少的條件下,卵巢切除后的小鼠海馬和前額葉組織內(nèi)神經(jīng)遞質(zhì)的水平發(fā)生了許多明顯改變,尤其是色氨酸通路中5-HT和N-乙酰五羥色胺水平明顯下降;犬尿素和犬尿胺酸水平均明顯升高。GABA通路中,琥珀酸(SA)水平明顯降低。可見(jiàn)在抑郁狀態(tài)下,雌激素水平與腦內(nèi)神經(jīng)遞質(zhì)有著密切聯(lián)系,影響了抑郁癥的發(fā)生發(fā)展。
[Abstract]:On the background of severe depression (MDD) is a kind of mental disease common multiple, adult prevalence rate is estimated at 5%-13%, in particular between men and women there is a great difference in the prevalence, the prevalence of female is about 1.5-3 times of the male. Due to the complex physiological and pathological factors, the prevalence of this huge the rate of gender differences has not been well established. But it is certain that sex hormones play an important role in the research on sex hormones may provide a breakthrough for emotional disorders prevalence in men and women. Estradiol (E2) are the main bioactive components of estrogen in vivo. There are mainly three forms: 2-3% 40-60% and albumin in the free state; and the two kinds of nodes, is a form of.40-60% estrogen exerts its biological activity in vivo and to sex hormone binding globulin (SHBG). With this kind of form is not play a biological role. A large number of studies show that estradiol play an important role in emotional disorders, so the detection of serum estrogen level in patients with severe depression in women, especially the bioactive estradiol level is very important, and we can further understand the changes of estrogen level on the nerve neurotransmitters related metabolites. Objective to detect the serum estradiol in female patients of severe depression and sex hormone binding globulin (SHBG) levels, understand the symptoms of biologically active estradiol levels and clinical relation, further combined with the ovariectomized animal model to investigate the effect of estrogen on various neurotransmitter related metabolites in the pathogenesis of severe depression methods. This experiment is divided into 3 parts of 1. severe depression female patients and healthy controls serum estradiol and women Hormone binding globulin (SHBG) levels detected by chemiluminescence microparticle immunoassay method, buy estradiol and sex hormone binding globulin standard and assay kit for.2. experimental operation to construct the evaluation model of ovariectomized mice and its quality by using automatic analyzer, including the detection of serum estradiol in ovariectomized mice the level of sucrose preference and weight measurement, detection of field test and forced swimming test.3. in ovariectomized mice hippocampus and prefrontal neurotransmitter related metabolites. The main open tryptophan pathway, detection of neural pathway and GABA pathway of catecholamine metabolites. Results the serum neurotransmitter 1. heavy depression in women with estradiol levels compared with healthy control women decreased P0.01; sex hormone binding control women did not significantly alter the.2. ovariectomized animal model globulin levels and health Built in ovariectomized mice serum estradiol level was significantly lower than normal control mice, p0.01. further detection model of animal behavior found in ovariectomized mice than normal mice in control group decreased sucrose preference, P0.05; body weight increased significantly, p0.05. open field experiment, ovariectomized mice compared with control mice horizontal movement and vertical score sports scores did not change significantly. In the forced swimming test found in ovariectomized mice compared with control mice real time and total immobility time% was significantly increased, p0.05.3. nerve in the ovariectomized rat tryptophan pathway in neurotransmitter metabolite levels compared with normal control was decreased obviously in mice most. Such as 5-HT were decreased obviously in hippocampus and prefrontal P0.05; five (n-as) n- acetyl serotonin levels were significantly decreased in the prefrontal lobe, P 0.05. also can be obviously found in the hippocampus of kynurenine (KYN) and kynurenine (kya) levels were significantly elevated in p0.05., gamma aminobutyric acid (GABA) pathway, can be found after ovariectomy prefrontal lobe and hippocampus in mice than normal group in succinic acid (SA) levels significantly decreased, P0.05; in the prefrontal lobe of glutathione (GSH) levels were significantly lower than normal, p0.05. in catecholamine pathway in ovariectomized mice compared with normal control mice hippocampus and prefrontal lobe related to neurotransmitter metabolites did not occur obvious change. Conclusion the level of serum estradiol in female patients with 1. severe depression significantly decreased, SHBG levels did not change significantly, so it has the biological activity in vivo in patients with severe depression of female estradiol level decreased significantly, reveals the changes in female patients with severe depression estradiol levels and depression. The development of.2. after ovariectomy, estrogen level decreases under the condition of mice after resection of ovary showed depression like behavior is more obvious. For example, the sucrose preference significantly reduced the degree of mice, body weight increased significantly, the forced swimming test in real time significantly increased.3. reduction in estrogen conditions, neurotransmitter after ovariectomy the mice in the hippocampus and prefrontal organization level has undergone many changes significantly, especially 5-HT and N- amino acid pathway in five acetyl serotonin levels decreased significantly; kynurenine and kynurenine levels were significantly elevated in the.GABA pathway, succinic acid (SA) levels were significantly decreased. Visible in the depression, neurotransmitter the level of estrogen in the brain are closely linked, affecting the development 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】：2016
【分類(lèi)號(hào)】：R749.4

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