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基于UPLC-Q/TOF MS技术的痛风患者血清代谢组学研究
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田力,杨宝,胡雪黎,杜桂艳,唐生尧,刘国生 1. 风湿性疾病发生与干预湖北省重点实验室(湖北民族大学)湖北 恩施 445000 2. 湖北民族大学 武陵山中药材检验检测中心湖北 恩施 445000 3. 湖北民族大学 医学部湖北 恩施 445000 4. 恩施市妇幼保健院 检验科湖北 恩施 445000 5. 湖北民族大学附属民大医院 医学检验科湖北 恩施 445000 
基金项目:风湿性疾病发生与干预湖北省重点实验室项目(PT022105);恩施州指导性项目(E20210033)
中文摘要:采用超高效液相色谱-飞行时间质谱联用技术(UPLC-Q/TOF MS)对恩施土家族苗族自治州60例健康志愿者(对照组)和65例痛风患者(痛风组)的血清样本建立代谢图谱,基于主成分分析及正交偏最小二乘判别分析对所得数据进行模式识别,并结合变量权重投影分析及火山图筛选出痛风患者的血清代谢标志物。通过数据分析和数据库检索,共筛选出63种差异代谢物,其中27种代谢物显著上调(P < 0.05),36种代谢物显著下调(P < 0.05),主要包括甘油磷脂类、氨基酸类及胆碱等成分。首先,对以上差异代谢物进行受试者工作特征曲线(ROC)分析,其中曲线下面积(AUC)大于0.8的14种代谢物是诊断效能较好的代谢物;然后对筛选的63种差异代谢物进行代谢通路富集分析,以 Impact > 0.1且P < 0.05为标准,得到影响最大的代谢通路主要有甘油磷脂代谢、醚性脂质代谢、亚油酸代谢、半胱氨酸和蛋氨酸代谢、花生四烯酸代谢及戊糖和葡萄醛酸的互相转化等。综上,痛风患者和健康对照人群的血清代谢水平有明显差异,差异代谢物的鉴定为痛风的发病机制和早期筛查提供了实验依据。
中文关键词:痛风  代谢组学  UPLC-Q/TOF MS  生物标志物  血清
 
Metabolomic Investigation on Serum of Gout Patients Based on Ultra-high Performance Liquid Chromatography-Quadrupole Time-of-flight Mass Spectrometry
Abstract:An ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF MS) was applied to establish a metabolic map on the serum samples of 60 healthy volunteers(control group) and 65 gout patients(gout group),to investigate the serum metabolomics differences between patients suffering from gout and healthy volunteers to find potential serum biomarkers.The obtained data were pattern-identified based on principal component analysis and orthogonal partial least squares analysis.The serum metabolic markers for gout patients were screened by the combination of variable weight projection analysis and a volcanic map.Through data analysis and database search,a total of 63 different metabolites were screened,27 metabolites were significantly up-regulated(P < 0.05),while 36 metabolites were significantly down-regulated(P < 0.05),mainly including glycerol phospholipids,amino acids and choline,etc.Firstly,conducting ROC curve analysis on the obtained differential metabolites,14 metabolites with AUC area greater than 0.8 were the better metabolites for diagnosis.Then,63 differential metabolites screened were analyzed for metabolic pathway enrichment.Impact > 0.1 and P < 0.05 were taken as the standards,the obtained metabolic pathway primarily included glycerol phospholipid metabolism,ether lipid metabolism,linoleic acid metabolism,cysteine and methionine metabolism,arachidonic acid metabolism and the mutual conversion of pentasaccharide and glucuronic acid.Results showed that there were apparent differences in serum metabolism levels between gout patients and healthy control populations,and the identification of differential metabolites provided an experimental basis for the pathogenesis and early screening of gout.
Key Words:gout  metabolomics  UPLC-Q/TOF MS  biomarkers  serum
引用本文:田力,杨宝,胡雪黎,杜桂艳,唐生尧,刘国生.基于UPLC-Q/TOF MS技术的痛风患者血清代谢组学研究[J].分析测试学报,2023,(5):596-604.
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