基于GC-TOFMS和UPLC-QTOFMS代谢组学分析平台对轻微型肝性脑病特异性代谢物谱的分析  

Analysis of specific metabolite profiling of minimal hepatic encephalopathy based on metabolomics analytical platforms of GC-TOFMS and UPLC-QTOFMS

作　　者：黄国初[1] 王萌[1] 杨小徽[2] 姚凡[1] 钟宇[2] 姚春[2] 

机构地区：[1]广西中医药大学第一附属医院,南宁530023 [2]广西中医药大学,南宁530001

出　　处：《临床肝胆病杂志》2016年第1期139-142,共4页Journal of Clinical Hepatology

基　　金：国家自然科学基金项目(81160439)

摘　　要：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 encephalopathy （ MHE）, identify the specific biomarkers of MHE, and explore the method for early diagnosis of MHE. 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- mine the biomarkers for MHE. Results In combination of the modeling analysis with PCA and OPLS - DA, the results from univariate t 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- olites and 18 up -regulated metabolites in the patients with MHE compared with healthy volunteers. Conclusion Serum metabolomics ana- 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.

关 键 词：肝性脑病 质谱分析法 早期诊断 

分 类 号：R575.3[医药卫生—消化系统]