非酒精性脂肪性肝病不同表型的代谢组学研究被引量：6

The metabolomics analysis of liver and serum in different phenotypes of non-alcoholic fatty liver disease

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摘要目的本研究旨在研究非酒精性脂肪性肝病(NAFLD)不同表型在代谢水平的变化,从而探索其所涉及的生物学过程并为临床提供合适的诊断生物标记物。方法使用高脂饲料,蛋氨酸胆碱缺乏饲料和链脲佐菌素腹腔注射建立单纯性脂肪肝(NAFL)、非酒精性脂肪性肝炎(NASH)和NAFL伴随2型糖尿病(NAFL+T2DM)的大鼠模型。通过液相色谱-四级杆飞行时间质谱在大鼠的肝脏和血清中检测差异表达的代谢物。结果 NAFL组大鼠肝脏出现轻度的脂肪变性并出现糖耐量异常;NASH组大鼠肝脏出现显著的大泡性脂肪变和炎症浸润,但空腹血糖和空腹胰岛素正常;NAFL+T2DM大鼠肝脏脂肪变以小泡性为主,并且空腹血糖和胰岛素显著升高(P<0.05)。代谢组学发现在NAFL组、NASH组和NAFL+T2DM组中,分别有57、49和60种肝脏代谢物发生变化,以及50、68和41种血清代谢物发生变化;它们主要参与脂质代谢和脂肪酸代谢。有17种肝脏代谢物和4种血清代谢物在NAFL,NASH和NAFL+T2DM组发生了相同的变化,其中只有硬脂酰肉毒碱含量在大鼠的肝脏和血清中都显著升高(P<0.05)。结论NASH、NAFL和NAFL+T2DM都出现了脂质和脂肪酸的代谢紊乱,硬脂酰肉毒碱在NAFLD的不同表型中都稳定升高,可以为临床提供一个更敏感的NAFLD诊断生物标记物。 Objective To investigate the metabolic changes in different phenotypes of non-alcoholic fatty liver disease（NAFLD）and the metabolic pathway involved in NAFLD,and to find an applicable biomarker in clinical diagnosis.Methods The high fat diet（HFD）,methionine and choline deficient（MCD）diet and streptozocin（STZ）were used for the establishment of non-alcoholic fatty liver（NAFL）non-alcoholic steatohepatitis（NASH）and NAFL＋type 2 diabetes mellitus（T2DM）rat models,respectively.The liquid chromatography-mass spectrometry（LC-MS）was performed in rat liver and serum to measure the metabolic changes in the three phenotypes of NAFLD.Results The NAFL group showed mild hepatic and metabolic lesion,while the NASH group showed severe histological changes accompanied with rear glycolmetabolic disturbances,and NAFL＋T2DM group exhibited severe glycol-metabolic disorders accompanied with mild liver injury.The metabolomics analysis found 57,49 and 60 hepatic metabolites,50,68 and 41 serum metabolites significantly altered in NAFL,NASH and NAFL ＋ T2 DM groups,respectively,which mainly involved in lipid and fatty acid metabolism.There were 17 liver metabolites and 4 serum metabolites were commonly changed in NAFL,NASH and NAFL＋T2DM groups,among which stearoylcarnitine was the only one up-regulated both in rat liver and serum（P〈0.05）.Conclusion The lipid and fatty acid metabolism are disturbed in NASH,NAFL and NAFL＋ T2 DM groups,and stearoylcarnitine are increased in different phenotypes of NAFLD.

作者刘晓琳明雅南张静怡曾民德茅益民

机构地区上海交通大学医学院附属仁济医院消化内科

出处《肝脏》 2015年第2期95-100,共6页 Chinese Hepatology

基金 "十二五"科技重大专项(2012ZX09303-001 2012ZX09401004)

关键词非酒精性脂肪性肝病代谢组学硬脂酰肉毒碱生物标记物 Non-alcoholic fatty liver disease Metabolomics Stearoylcarnitine Biomarker

分类号 R575.5 [医药卫生—消化系统]

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