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基于超高效液相色谱-串联飞行时间质谱联用技术的非酒精性脂肪性肝病患者血清代谢组学分析 被引量:1

Serum metabolomics analysis of patients with nonalcoholic fatty liver disease based on ultra performance liquid chromatography-tandem time-of-flight mass spectrometry
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摘要 目的 通过对非酒精性脂肪性肝病(NAFLD)患者血清中代谢物的差异性表达谱及功能代谢组学的研究,确立与NAFLD发生发展密切相关的特异性生物标志物。方法 采用超高效液相色谱-串联飞行时间质谱联用(UHPLC-QTOF/MS)技术对入选的NAFLD患者和健康对照组进行极性小分子代谢产物检测分析,通过与数据库中代谢物的保留时间、分子质量(分子质量误差在<25 ppm内)、二级碎裂谱图、碰撞能等信息进行匹配,对生物样本中的代谢物进行结构鉴定,并对鉴定结果进行严格的人工二次核对、确认。结果 以严格的OPLS-DA VIP>1和P <0. 05为显著性差异代谢物筛选标准,共筛选、鉴定出12种差异代谢物。与健康者相比,NAFLD患者体内肉豆蔻酸、棕榈酸等5种代谢物上调;马尿酸、N-二十二碳酰-4-鞘氨醇-1-O-磷酰胆碱等7种代谢物下调;且此结果可能与脂肪酸生物合成、脂肪酸伸长率、胆固醇代谢等通路相关。结论 NAFLD患者与健康对照人群在血清代谢水平上具有明显差异,并用代谢组学的方法来研究了NAFLD差异代谢物的变化规律,为NAFLD的诊治和研究提供了新的方法。 Objective The differential expression profile and functional metabolomics of metabolites in serum of patients with non-alcoholic fatty liver disease(NAFLD)were studied to establish specific biomarkers closely related to the occurrence and development of NAF LD.Methods The polar small molecular metabolites of selected NAFLD patients and healthy controls were detected and analyzed by using ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry(UHPLC-Q-TOF/MS)technology.By matching the retention time,molecular mass(molecular mass error within<25 ppm),secondary fragmentation spectnun,collision energy and other information of metabolites from the database,the structure of metabolites in biological samples was identified,and strict manual secondary verification and confirmation was conducted on the identification results.Results Using OPLS-DA VIP>1 and P<0.05 as the screening criteria for significant differential metabolites,a total of 12 differential metabolites were screened and identified.Compared with healthy subjects,5 metabolites including Myristic acid and Palmitic acid were up-regulated in NAFLD patients.7 kinds of metabolin including Hippuric acid,N-Docosanoyl-4-sphingenyl-1-0-phosphorylcholine were down-regulated.The results may be related to fatty acid biosynthesis,fatty acid elongation,cholesterol metabolism and other pathways.Conclusion There were significant differences in serum metabolism between NAFLD patients and healthy controls,and the changes of differential metabolites in NAFLD were studied by using metabonomics,which provided a new method for the diagnosis and treatment of NAFLD.
作者 赵笔辉 王金瑜 孙丽丽 张倩 乐群燕 李聪亚 ZHAO Bi-hui;WANG Jin-yu;SUN Li-li;ZHANG Qian;LE Qun-yan;LI Cong-ya(Beilun District People's Hospital,Ningbo,Zhejiang 315800,China)
出处 《中国卫生检验杂志》 CAS 2021年第19期2380-2385,共6页 Chinese Journal of Health Laboratory Technology
关键词 非酒精性脂肪性肝病 超高效液相色谱-串联飞行时间质谱联用 代谢组学 生物标志物 Non-alcoholic fatty liver Ultra performance liquid chromatography-tandem time-of-flight mass spectrometry Metabolomics Biomarkers
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