基于~1H NMR的妊娠期糖尿病代谢组学研究

发布时间：2018-06-23 15:06

本文选题：基于NMR的代谢组学 + 妊娠期糖尿病(GDM)　；参考：《厦门大学》2014年硕士论文

【摘要】：代谢组学是20世纪90年代末期发展起来的一门新兴学科,它借助高通量、高灵敏度的现代分析技术,分析生物体中内源性代谢物的整体组成,并通过跟踪代谢物复杂、动态的变化,辨识和解析被研究对象的生理病理状态。妊娠期糖尿病(gestational diabetes mellitus, GDM)是糖尿病的一种独立类型,是在妊娠期特发的代谢性疾病。本文将基于核磁共振(NMR)的代谢组学方法应用于GDM的研究中,分析GDM志愿者和健康孕妇志愿者的血清和尿液中小分子代谢物的差异,探索GDM的生物标记物和受损代谢通路,为GDM的病理机制研究提供新的科学依据。本文的主要内容归纳如下：首先,详细综述了代谢组学方法在GDM研究中的应用,总结并列举了代谢组学在GDM研究中的优势。其次,应用1H NMR分析了GDM患者和健康孕妇血清和尿液的代谢轮廓,并结合多元统计分析发现：GDM患者的血清中葡萄糖、氧化三甲胺、琥珀酸和甘氨酸等代谢物含量明显升高；尿液中甘氨酸、二甲基甘氨酸、尿黑酸、N-甲基-烟酰胺(N-methylnicotinamide, NMND)等含量升高,而丙二酸、乙醇胺、苯乙酰谷氨酰胺(phenylacetylglutamine, PAG)、马尿酸、抗坏血酸等含量降低等现象。结果说明GDM不仅影响了机体的糖类、脂类和氨基酸的代谢,也导致了能量代谢以及肝肠循环等其他代谢系统的紊乱。尤其到了妊娠期糖尿病晚期,随着胰岛素抵抗作用增强,物质和能量的代谢也逐步增强,导致机体代谢进一步失衡,加重肝肾的负担,从而引起肝肾功能失调。基于NMR的代谢组学分析方法为探讨GDM的病理机制提供一个很好的技术平台,并将在GDM的早期诊断和个体化治疗等方面的研究具有广阔的应用前景。
[Abstract]:Metabonomics is a new discipline developed in the late 1990s. It uses modern analytical techniques with high throughput and high sensitivity to analyze the whole composition of endogenous metabolites in organisms, and it is complex by tracking metabolites. Dynamic changes, identification and analysis of the physiological and pathological state of the subjects studied. Gestational diabetes mellitus (gestational diabetes mellitus,) is an independent type of diabetes mellitus. In this paper, the nuclear magnetic resonance (NMR) based metabolomics method was applied to the study of GDM. The differences of small molecular metabolites in serum and urine between GDM volunteers and healthy pregnant women were analyzed, and the biomarkers and impaired metabolic pathways of GDM were explored. To provide a new scientific basis for the study of pathological mechanism of GDM. The main contents of this paper are summarized as follows: firstly, the application of metabonomics in GDM research is reviewed in detail, and the advantages of metabonomics in GDM research are summarized and enumerated. Secondly, the metabolic profiles of serum and urine of GDM patients and healthy pregnant women were analyzed by 1H NMR. The results of multivariate statistical analysis showed that the contents of glucose, trimethylamine oxide, succinic acid and glycine in serum of patients with GDM increased significantly. The contents of glycine, dimethyl glycine, N-methylated nicotinamide (NMND) in urine increased, while malonic acid, ethanolamine, phenylacetylglutamine (PAG), hippuric acid and ascorbic acid decreased. The results showed that GDM not only affected the metabolism of carbohydrate, lipids and amino acids, but also caused the disorder of energy metabolism and other metabolic systems such as liver and intestine circulation. Especially in the late gestational diabetes mellitus, with the increase of insulin resistance, the metabolism of substance and energy is gradually enhanced, which leads to the further imbalance of body metabolism, aggravating the burden of liver and kidney, thus causing the disorder of liver and kidney function. The method of metabolomics analysis based on NMR provides a good technical platform for discussing the pathological mechanism of GDM and will be widely used in the early diagnosis and individualized treatment of GDM.
【学位授予单位】：厦门大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.256;R445.2

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