慢性失眠症患者血清及尿液非靶向代谢组学特征分析  

Untargetted metabolomics of serun and urine among chronic insomnia disorder patients

作　　者：丁莹梅 马宾 刘晓芬 袁梅 DING Yingmei;MA Bin;LIU Xiaofen;YUAN Mei(不详;Department of Neurology,The Second Affiliated Hospital of Nanhua University,Hunan Hengyang 421200,China)

机构地区：[1]长沙泰康之家湘园康复医院,410000 [2]南华大学附属第二医院神经内科,421001

出　　处：《中国神经免疫学和神经病学杂志》2024年第6期441-447,共7页Chinese Journal of Neuroimmunology and Neurology

基　　金：湖南省卫生健康委高层次人才重大科研专项(R2023150);湖南省临床医学研究中心(2023SK4050);南华大学临床医学研究“4310”计划项目(20224310NHYCG08);湖南省卫健委一般资助课题(202203072849);湖南省自然科学基金面上项目(2022JJ30523)。

摘　　要：目的利用非靶向代谢组学技术对比慢性失眠症患者与健康人群在血清及尿液中的代谢组改变情况,为研究失眠症的病理学机制提供数据支持。方法纳入2021年2月至2021年10月就诊于南华大学附属第二医院慢性失眠症患者30例,另募集同期健康体检者30名为对照组。收集其血清及尿液制备样本后基于液相色谱质谱生物学技术做非靶向代谢组学分析。通过构建多元统计分析模型,筛选识别两组间在血清及尿液中的差异代谢物,并进行代谢通路富集分析从而对比失眠人群整体代谢改变情况。结果失眠组及健康组在血清及尿液中的代谢成分均存在差异,在血清及尿液中分别筛选到36种和65种差异代谢物,其中血清中反式-4-羟基-L-脯氨酸、2-氨基己二酸等和尿液中1-甲基腺嘌呤、N-(2,4-二甲基苯基)甲酰胺、肌肽等物质是慢性失眠症潜在诊断标志物。通路富集分析显示,失眠障碍在血清中主要存在氨基酸代谢异常,如丙氨酸代谢、天冬氨酸和谷氨酸代谢、脯氨酸代谢等。失眠相关的尿液代谢改变则主要涉及维生素B6代谢、咖啡因代谢、组氨酸代谢等。结论通过非靶向代谢组学技术识别出慢性失眠症患者血清及尿液中多种差异代谢产物和代谢通路,为失眠症临床监测与治疗提供了更多的切入点。Objective To compare the metabolomic changes in serum and urine between patients with chronic insomnia and healthy people by non-targeted metabolomics technology,and to provide data support for studying the pathological mechanism of insomnia.Methods Thirty patients with chronic insomnia and 30 healthy controls attending the Second Affiliated Hospital of Nanhua University from February 2021 to October 2021 were recruited.After collecting their serum and urine preparation samples,non-targeted metabolomics analysis was conducted based on liquid chromatography mass spectrometry biology.By constructing a multivariate statistical analysis model,we screened and identified the different metabolites in serum and urine between the two groups,and performed metabolic pathway enrichment analysis,so as to compare the overall metabolic changes in the insomnia population.Results The insomnia group and the healthy group had metabolic differences in serum and urine,and 36 and 65 differential metabolites were screened in serum and urine,respectively.Among them,trans-4-hydroxy-L-proline and 2-aminoadipic acid in serum,and 1-methyladenine,N-(2,4-dimethylphenyl)formamide,and carnosine in urine were potential diagnostic markers for chronic insomnia.Pathway enrichment analyses showed that insomnia disorders are mainly characterized by abnormalities of amino acid metabolism in serum,such as alanine metabolism,aspartate and glutamate metabolism,and proline metabolism.Insomnia-related alterations in urinary metabolism,on the other hand,mainly involve vitamin B6 metabolism,caffeine metabolism,and histidine metabolism.Conclusions A variety of differential metabolites and metabolic pathways in serum and urine of patients with chronic insomnia are identified by non-targeted metabolomics technology,which provides more entry points for clinical monitoring and treatment of insomnia.

关 键 词：非靶向代谢组学 慢性失眠症 血清 尿液 

分 类 号：R741[医药卫生—神经病学与精神病学]