抑郁状态下雌二醇与神经递质代谢物关系的初步研究

发布时间：2018-03-10 03:37

本文选题：重型抑郁　切入点：雌二醇　出处：《重庆医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：研究背景重型抑郁(MDD)是普遍多发的一种精神系统疾病,成人患病率据估计在5%-13%,尤其特殊的是男女之间存在着很大的患病率差异,女性患病率大约是男性的1.5-3倍。由于复杂的生理病理学因素,目前这种巨大的患病率性别差异仍未得到很好的阐释。但是可以肯定的是性激素在其中发挥了重要作用,有关性激素方面的研究有可能为情感障碍类疾病在男女患病率差异上提供一个突破口。雌二醇(E2)是雌激素中主要的生物活性成分,在体内主要以三种形式存在:2-3%呈游离状态;40-60%与白蛋白结和,这两种形式是雌激素在体内能够发挥生物学活性的形式。40-60%与性激素结合球蛋白(SHBG)相结合,这种形式是不能发挥生物学作用的。大量的研究表明雌二醇在情感障碍类疾病中发挥了重要作用,所以检测重型抑郁女性患者血清雌激素水平,特别是具有生物活性的雌二醇水平是十分有意义的,而且可以进一步了解雌激素水平的变化对神经递质相关代谢物的影响。目的通过检测女性重型抑郁病人血清雌二醇和性激素结合球蛋白(SHBG)水平,了解具有生物活性的雌二醇水平与临床症状间的联系,进一步结合卵巢切除动物模型来探讨雌激素在重型抑郁发病中对各种神经递质相关代谢物的影响。方法本实验总共分为3个部分1.重型抑郁女性患者和健康对照女性血清雌二醇和性激素结合球蛋白(SHBG)水平的检测,运用化学发光微粒子免疫检测法,购买雌二醇和性激素结合球蛋白标准品及测定试剂盒,运用全自动生化免疫分析仪进行实验操作。2.构建卵巢切除小鼠模型及其质量评价,包括卵巢切除后小鼠血清雌二醇水平的检测,糖水偏好和体重测量,旷场实验和强迫游泳实验。3.卵巢切除小鼠海马和前额叶神经递质相关代谢物的检测。主要进行了色氨酸通路,gaba通路和儿茶酚胺通路相关神经递质代谢物的检测。结果1.重型抑郁女性患者血清雌二醇水平较健康对照女性明显降低,p0.01;性激素结合球蛋白水平与健康对照女性没有明显改变。2.卵巢切除动物模型构建,卵巢切除后小鼠血清雌二醇水平较正常对照小鼠明显降低,p0.01。进一步检测模型动物的行为学发现卵巢切除后小鼠较正常对照组小鼠糖水偏好降低,p0.05;体重明显增加,p0.05。旷场实验中,卵巢切除后小鼠较正常对照小鼠水平移动得分和垂直运动得分均没有明显改变。在强迫游泳实验中发现卵巢切除后小鼠较正常对照小鼠不动总时间和不动时间%均明显增加,p0.05。3.在卵巢切除后小鼠色氨酸通路中的相关神经递质代谢物水平较正常对照小鼠多数发生了较为明显的下降。如5-ht在海马和前额叶内均发生了较为明显的下降,p0.05;n-乙酰五羟色胺(n-as)水平在前额叶内发生了明显下降,p0.05。另外可以明显的发现在海马内犬尿素(kyn)和犬尿胺酸(kya)水平均明显升高,p0.05。在γ-氨基丁酸(gaba)通路中,可以发现卵巢切除后小鼠较正常组小鼠前额叶和海马内琥珀酸(sa)水平明显降低,p0.05;在前额叶内谷胱甘肽(gsh)水平较正常组明显降低,p0.05。在儿茶酚胺通路中,卵巢切除小鼠较正常对照组小鼠海马和前额叶内神经递质相关代谢物并未发生较为明显的改变。结论1.重型抑郁女性患者血清雌二醇水平明显降低,SHBG水平并未明显改变,因此在重型抑郁女性患者体内具有生物学活性的雌二醇水平明显降低,揭示了在重型抑郁女性患者体内雌二醇水平的变化参与了抑郁症的发生发展。2.卵巢切除后,雌激素水平降低的条件下,卵巢切除后的小鼠表现出了较为明显的抑郁样行为。比如小鼠糖水偏好程度明显降低,体重明显增加,强迫游泳实验中不动时间明显增加。3.在雌激素减少的条件下,卵巢切除后的小鼠海马和前额叶组织内神经递质的水平发生了许多明显改变,尤其是色氨酸通路中5-HT和N-乙酰五羟色胺水平明显下降;犬尿素和犬尿胺酸水平均明显升高。GABA通路中,琥珀酸(SA)水平明显降低。可见在抑郁状态下,雌激素水平与脑内神经递质有着密切联系,影响了抑郁症的发生发展。
[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.

【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.4

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