目的：分析对比健康志愿者及轻微型肝性脑病（MHE ）患者的血清代谢物谱，确立MHE特异性生物标志物，探索MHE早期诊断方法。方法收集2013年10月－2014年10月广西中医药大学第一附属医院收治的乙型肝炎肝硬化导致的MHE患者29例（MHE组）和同期本院健康体检者50例（NC组），运用气相色谱－飞行时间质谱仪（GC－TOFMS）和超高压液相色谱－四级杆－飞行时间质谱仪（UPLC－QTOFMS）检测受试者血清样本中的代谢物，并通过主成分分析（PCA）、正交偏最小二乘法－判别分析（OPLS－DA）进行多维统计分析，结合单维t检验进行组间比较，最终确定与MHE相关的生物标志物。结果对2组进行了PCA和OPLS－DA建模分析，结合单维t检验结果，并参照模型中的VIP值，在2组血清中找到27种可能的MHE 特异性生物标志物。根据OPLS－DA模型中MHE组和NC组代谢物质的比值可见，与健康志愿者相比，在MHE患者血清中下调的物质有9种，上调的物质有18种。结论基于GC－TOFMS和UPLC－QTOFMS平台的血清代谢组学分析技术可同时检测患者血清中多种代谢物质，有助于研究MHE的发病机制。本研究建立的OPLS－DA诊断模型可用于鉴别健康人群与MHE患者，有望用于MHE的早期诊断。%Objective To analyze and compare the serum metabolite profiling of healthy volunteers and patients with minimal hepatic en-cephalopathy(MHE),identifythespecificbiomarkersofMHE,andexplorethemethodforearlydiagnosisofMHE.Methods Twenty-nine patients with MHE caused by hepatitis B cirrhosis who were admitted to First Affiliated Hospital of Guangxi University of Chinese Medi-cine (MHE group)from October 2013 to October 2014,as well as 50 healthy volunteers who received physical examinations in this hospital (NC group)during the same period,were collected.Gas chromatography and time-of-flight mass spectrometry (GC-TOFMS)and ultra-high-pressure liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-QTOFMS)were applied to determine the metabolites in serum samples.Principal component analysis (PCA)and orthogonal partial least squares-discriminant analysis (OPLS-DA)were applied for multivariate statistical analysis,and univariate t test was applied for comparison between the two groups,so as to deter-minethebiomarkersforMHE.Results IncombinationofthemodelinganalysiswithPCAandOPLS-DA,theresultsfromunivariatet test,and vasoactive intestinal peptide (VIP)value in the models,a total of 27 possible specific biomarkers for MHE were found in serum in the two groups.According to the fold change between MHE group and NC group in OPLS-DA model,there were 9 down-regulated metab-olitesand18up-regulatedmetabolitesinthepatientswithMHEcomparedwithhealthyvolunteers.Conclusion Serummetabolomicsana-lytical platforms such as GC-TOFMS and UPLC-QTOFMS can detect a variety of metabolites in serum,which can be of help to explore the pathogenesis of MHE.In addition,the diagnostic model OPLS-DA established in this study can differentiate between the normal population and patients with MHE,which may be applied for early diagnosis of MHE.
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