基于代谢组学的抑郁症患者粪便研究

发布时间：2018-01-23 12:40

本文关键词： 抑郁症代谢组学诊断生物标志物　出处：《重庆医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：背景抑郁症是一种普遍的精神疾病,患病率高和复发率高是该病主要特点。抑郁症防治面临两个主要困难:发病机制不明确和缺乏客观的实验室诊断方法。目前为止,抑郁症发病机制依旧众说纷纭,主要包括去甲肾上腺素(Nor epinephrine,NE)及其受体学说、5-羟色胺(5-hydroxytryptamine,5-HT)及其受体学说、多巴胺(dopamine,DA)及其受体学说、乙酰胆碱(acetylcholine,Ach)能学说等。目前抑郁症的主要诊断方式是由医生以患者的临床症状为依据做出主观判断。然而抑郁症患者的临床症状差异性很大,因此以患者临床症状为诊断依据的诊断方法准确率很不理想。综上,开展抑郁症粪便相关生物标志物的研究不但有助于揭示抑郁症的发病机制,而且是对血液、尿液、脑脊液等检测方法的有效补充,给临床诊断带来便利。代谢组学是在后基因时代系统生物学的重要组成部分,它能够测量生物样本中的小分子代谢物质。本课题组前期对抑郁动物模型代谢组学研究提示中枢以及外周的代谢紊乱可能与抑郁症发病相关。鉴于抑郁动物模型不能完全模拟人的抑郁发作,因此进一步开展抑郁症患者的代谢组学分析仍十分必要。目的本次研究以核磁共振(NMR)代谢组学实验方法为基础,对抑郁症患者与正常对照者粪便进行分析,筛选出与抑郁症相关的粪便差异代谢物质,并进一步分析相关差异代谢物质的代谢通路、分子网络、分子功能,初步揭示抑郁症粪便差异代谢物在抑郁症发病过程中的作用。方法收集样本:71例首发的抑郁症患者和82例正常对照者粪便,用于筛选抑郁症相关的潜在生物标志物;样本检测:通过核磁共振(nmr)技术检测粪便中的代谢物质;数据分析:采用分步优化法分析抑郁症组与正常对照组,筛选抑郁症相关的粪便差异代谢物质。结果:采用基于nmr的代谢组学研究技术方法,分析对比71例首发的抑郁症患者与82例正常对照者的粪便代谢谱。经过多元分析,我们发现;乙酰乙酸、天门冬氨酸、肌酸、二甲基甘氨酸、乙醇胺、谷氨酰胺、谷氨酰胺、甘油胆碱磷酸、甘氨酸、乳酸、赖氨酸、丙二酸、甲胺、肌醇、牛磺酸、苏氨酸、三甲胺在抑郁症患者中表达量升高;乙酸、腺嘌呤、丁酸在抑郁症患者中表达量降低。功能分析发现这些差异代谢物质主要与“脂质代谢紊乱”、“小分子生物化学紊乱”以及“氨基酸代谢紊乱”相关。结论:通过对抑郁症患者和正常对照者粪便的代谢组学分析,发现了一系列抑郁症相关的粪便差异代谢物质。通过对这些差异代谢物质的代谢通路、分子功能以及分子网络分析,为后续抑郁症的病理生理研究、发病机制研究以及生物标志物的开发提供依据。
[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.
【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;R446.13

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