基于气相色谱-质谱联用技术的痛风病人血清代谢特征分析

Analysis of Serum Metabolic Characteristics in Patients with Gout Using Gas Chromatography-Mass Spectrometry

痛风是一组仅见于人类的异质性疾病,随着时间的推移,将导致慢性关节炎并逐渐致残。该研究将基于气相色谱-质谱联用技术(GC-MS)的代谢组学方法应用于痛风病人的血清代谢特征分析。首先利用GCMS获得痛风病人和健康人的血清代谢指纹图谱,采用多变量统计分析对所得数据进行分析。主成分分析(PCA)得分图显示,痛风病人与健康人的血清代谢谱有差异。通过偏最小二乘-判别分析(PLS-DA)对样品进行进一步分型,根据模型的变量重要性因子(VIP值)及非参数检验结果筛选差异代谢物。共筛选出43种可能与痛风相关的代谢物,并对其中22个变量进行结构鉴定,主要包括丙二醇、2,3-二羟基丁酸、2,4-二羟基丁酸、赤藓糖醇、苏糖醇、苏糖酸、阿拉伯糖醇、D-葡萄糖酸、肌醇、次黄嘌呤、尿酸、尿苷、3-羟基-3-甲基丁酸、鸟氨酸、吲哚-3-乳酸、单乙醇胺、甘油、甘油酸、月桂酸及亚油酸等代谢物。与健康人相比,痛风病人的糖代谢、核苷酸代谢、氨基酸代谢及脂类代谢均发生了明显的紊乱。这些结果将为痛风临床诊断及治疗提供重要依据。

Gout is a highly heterogeneous disease which occurs only in human being,it would cause gouty arthritis,and even lead to disability. There could be obvious alterations of metabolites in the serum of the patient with gout,and the discovery of metabolic characteristics may be helpful for the clinical diagnosis and treatment of gout. A gas chromatography- mass spectrometry（ GC- MS） based metabolic profiling method was employed to analyze the distinctive metabolic patterns of serum in gout patients. Serum samples collected from 29 gout patients and 26 healthy controls were analyzed. The principal component analysis（ PCA） and partial least squares discriminant analysis（ PLS- DA） were used to assess the metabolic data. Marked differences between gout patients and healthy controls were shown in PCA score plot. Variable importance for project values（ VIP） and Student＇s t-test were combined to pick out the significant metabolic changes. Compared with that of the control group,the serum metabolic characteristics of the gout group were featured by increased levels of metabolites related to nucleotide metabolism（ hypoxanthine,uric acid and uridine）,carbohydrate metabolism（ 2,3-dihydroxybutyrate,D-threitol,D-gluconic acid,myo-inositol,etc.） and amino acid metabolism（ 3-hydroxy-3-methylbutyrate,L-ornithine and indole-3-lactic acid）,decreased levels of lipids（ monoethanolamine,glycerol,glyceric acid, etc.）, glycine and hypotaurine. The preliminary results suggest that GC- MS based metabolic profiling method appears to be a useful tool in the exploration of the serum metabolic characteristics of gout. These revealed disease-associated metabolic perturbations involved in multiple metabolic pathways including purine metabolism and the urea cycle,which could help to elucidate the pathogenesis of gout and provide a potential aid for the accurate diagnosis or treatment of gout.