摘要目的 基于气相色谱质谱的代谢组学分析方法,研究高脂血症性胰腺炎(HLP)患者尿样.通过对其尿样代谢物组的分析和生物标记物的发现,寻找HLP的代谢变化,探讨代谢组学在急性胰腺炎(AP)中的应用.方法 取24例HLP患者尿样及40例年龄、性别匹配的正常健康人尿样,样品经预处理、衍牛和气相色谱质谱分析后,利用正交偏最小方差判别分析(OPISA-DA)的方法,观察健康组和HLP组的代谢轮廓差异.结果 上述方法能清晰地将HLP患者和健康人样本分开,通过NIST、Wiley等谱库搜索分析了21个代谢物(可信度>700).其中用标准品鉴定之后,发现与健康组比较HLP患者尿样中烟酸、乌头酸、柠檬酸、马尿酸、对一羟基苯乙酸、对-羟基苯丙酸含量下降;色氨酸、酪氨酸、酪胺、棕榈油脂、硬脂酸等物质含量上升.代谢组学研究显示HLP患者三羧酸循环、肠道菌群结构、脂肪代谢及氨基酸代谢等发生改变.结论 HLP患者和正常人尿样代谢谱之间存在差异,而且可能从代谢组学分析中找出特异的标志性代谢产物,阐释该疾病的代谢变化;表明利用代谢组学研究尿液中的代谢物,可以为HLP的诊断和发病机制提供一个可借鉴的手段;代谢组学分析是一种有良好发展前景的研究方法.
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abstractsObjective Metabonomics method based gas chromatography-mass spectrometry (GC/MS)were used to analyze the urine samples of patients with hyperlipidemic pancreatitis (HLP) to describe the characteristics of metabolism changes of HLP,identify potential biomarkers,and investigate the role of metabonomics study in the management of AP.Methods 24 patients of HLP and 40 age,sex matched volunteers were enrolled and their urine samples were collected.The urine samples underwent preparation,derivation and GC/MS analysis,Orthogonal-Projection to Latent Structures-Discriminant Analysis (OPLS-DA)were performed to detect the metabolic profile difference between the HLP and control group.Results HLP patients can be precisely distinguished from healthy controls.21 metabolites (credibility > 700 ) were identified using the reference compounds available in the libraries of NIST and Wiley.It was identified that levels of nicotinic acid,aconitie acid,citric acid,hippurie acid,hydroxyphenylacetic acid,hydroxyphenylpropionicacid were decreased,while the levels of tryptophan,tyrosine,tyramine,16-hexadecanoic acid,18octadecanoie acid were increased.It was also suggested that there was change in tricarboxylic acid cycle and gut bacterial flora,as well as fat metabolism and metabolism of amino acid.Conclusions There are differences between healthy controls and HLP patients in the term of GC/MS metabolic profiling,and the biomarkers in the metabolites could be found through metabonomics analysis,and the mechanisms of the metabolic changes could be explored.It was noted that the research of metabolites in the urine samples may be a useful tool to help diagnose and understand the pathogenesis of HLP.Metabonomics analysis is a promising research method.
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