本文關鍵詞： 抑郁癥 代謝組學 診斷 生物標志物　出處：《重慶醫(yī)科大學》2016年碩士論文　論文類型：學位論文

【摘要】：背景抑郁癥是一種普遍的精神疾病,患病率高和復發(fā)率高是該病主要特點。抑郁癥防治面臨兩個主要困難:發(fā)病機制不明確和缺乏客觀的實驗室診斷方法。目前為止,抑郁癥發(fā)病機制依舊眾說紛紜,主要包括去甲腎上腺素(Nor epinephrine,NE)及其受體學說、5-羥色胺(5-hydroxytryptamine,5-HT)及其受體學說、多巴胺(dopamine,DA)及其受體學說、乙酰膽堿(acetylcholine,Ach)能學說等。目前抑郁癥的主要診斷方式是由醫(yī)生以患者的臨床癥狀為依據(jù)做出主觀判斷。然而抑郁癥患者的臨床癥狀差異性很大,因此以患者臨床癥狀為診斷依據(jù)的診斷方法準確率很不理想。綜上,開展抑郁癥糞便相關生物標志物的研究不但有助于揭示抑郁癥的發(fā)病機制,而且是對血液、尿液、腦脊液等檢測方法的有效補充,給臨床診斷帶來便利。代謝組學是在后基因時代系統(tǒng)生物學的重要組成部分,它能夠測量生物樣本中的小分子代謝物質(zhì)。本課題組前期對抑郁動物模型代謝組學研究提示中樞以及外周的代謝紊亂可能與抑郁癥發(fā)病相關。鑒于抑郁動物模型不能完全模擬人的抑郁發(fā)作,因此進一步開展抑郁癥患者的代謝組學分析仍十分必要。目的本次研究以核磁共振(NMR)代謝組學實驗方法為基礎,對抑郁癥患者與正常對照者糞便進行分析,篩選出與抑郁癥相關的糞便差異代謝物質(zhì),并進一步分析相關差異代謝物質(zhì)的代謝通路、分子網(wǎng)絡、分子功能,初步揭示抑郁癥糞便差異代謝物在抑郁癥發(fā)病過程中的作用。方法收集樣本:71例首發(fā)的抑郁癥患者和82例正常對照者糞便,用于篩選抑郁癥相關的潛在生物標志物;樣本檢測:通過核磁共振(nmr)技術檢測糞便中的代謝物質(zhì);數(shù)據(jù)分析:采用分步優(yōu)化法分析抑郁癥組與正常對照組,篩選抑郁癥相關的糞便差異代謝物質(zhì)。結(jié)果:采用基于nmr的代謝組學研究技術方法,分析對比71例首發(fā)的抑郁癥患者與82例正常對照者的糞便代謝譜。經(jīng)過多元分析,我們發(fā)現(xiàn);乙酰乙酸、天門冬氨酸、肌酸、二甲基甘氨酸、乙醇胺、谷氨酰胺、谷氨酰胺、甘油膽堿磷酸、甘氨酸、乳酸、賴氨酸、丙二酸、甲胺、肌醇、牛磺酸、蘇氨酸、三甲胺在抑郁癥患者中表達量升高;乙酸、腺嘌呤、丁酸在抑郁癥患者中表達量降低。功能分析發(fā)現(xiàn)這些差異代謝物質(zhì)主要與“脂質(zhì)代謝紊亂”、“小分子生物化學紊亂”以及“氨基酸代謝紊亂”相關。結(jié)論:通過對抑郁癥患者和正常對照者糞便的代謝組學分析,發(fā)現(xiàn)了一系列抑郁癥相關的糞便差異代謝物質(zhì)。通過對這些差異代謝物質(zhì)的代謝通路、分子功能以及分子網(wǎng)絡分析,為后續(xù)抑郁癥的病理生理研究、發(fā)病機制研究以及生物標志物的開發(fā)提供依據(jù)。
[Abstract]:Background Depression is a common mental disorder. High prevalence and high recurrence rate are the main characteristics of the disease. There are two main difficulties in the prevention and treatment of depression: unclear pathogenesis and lack of objective laboratory diagnostic methods. The pathogenesis of depression is still controversial, mainly including norepinephrine ne) and its receptor theory. 5-hydroxytryptamine (5-HT) and its receptor theory, dopamine dopamine (DAA) and its receptor theory. Acetylcholine acetylcholine. At present, the main way of diagnosis of depression is to make subjective judgment based on the clinical symptoms of the patients. However, the clinical symptoms of patients with depression are very different. Therefore, the diagnostic accuracy based on the clinical symptoms of patients is not ideal. In summary, the research of depressive stool biomarkers is not only helpful to reveal the pathogenesis of depression, but also to the blood. The effective supplement of urine, cerebrospinal fluid and other detection methods has brought convenience to clinical diagnosis. Metabolomics is an important part of system biology in the post-gene era. It can measure the metabolites of small molecules in biological samples. Our previous studies on metabolomics of animal models of depression suggest that central and peripheral metabolic disorders may be associated with the onset of depression. Can't completely mimic a person's depression. Therefore, it is necessary to further develop the metabonomics analysis in patients with depression. Objective this study is based on the experimental method of nuclear magnetic resonance imaging (NMR) metabolomics. The feces of depressive patients and normal controls were analyzed to screen out the fecal differential metabolites related to depression and to further analyze the metabolic pathways molecular networks and molecular functions of related differential metabolites. Methods the feces of 71 first-episode depression patients and 82 normal controls were collected. For screening potential biomarkers associated with depression; Sample detection: nuclear magnetic resonance (NMR) technique was used to detect metabolites in feces. Data analysis: the depressive group and the normal control group were analyzed by stepwise optimization method to screen the depression-related faecal differential metabolites. Results: the technique of metabolomics based on nmr was used. Fecal metabolic profiles of 71 first-episode depression patients and 82 normal controls were analyzed and compared. Acetic acid, aspartic acid, creatine, dimethyl glycine, ethanolamine, glutamine, glutamine, glycerol choline phosphate, glycine, lactic acid, lysine, malonic acid, methylamine, inositol, taurine. The expression of threonine and trimethylamine was increased in patients with depression. The expression of acetic acid, adenine, butyric acid in depression patients decreased. Functional analysis found that these differential metabolites were mainly associated with "lipid metabolism disorder". Conclusion: the metabolomics of feces in patients with depression and normal controls is related to "small molecular biochemical disorders" and "metabolic disorders of amino acids". A series of depressive related fecal differential metabolites were found. Through the analysis of the metabolic pathway, molecular function and molecular network of these differential metabolites, the pathophysiology of depression was studied. The study of pathogenesis and the development of biomarkers provide basis.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R749.4;R446.13

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