慢性乙型肝炎患者血清脂质组学研究  

Serum lipidomic analysis of patients with chronic hepatitis B

作　　者：杨蕊旭[1] 胡春秀[2] 陈国凤[3] 孙长贵[4] 孙婉璐[1] 陈光榆[1] 潘勤[1] 沈峰[1] 许国旺[2] 范建高[1] 

机构地区：[1]上海交通大学医学院附属新华医院消化内科暨脂肪肝诊治中心,上海市200092 [2]中国科学院大连化学物理研究所/中国科学院分离分析化学重点实验室 [3]解放军第302医院肝纤维化诊疗中心 [4]江苏省昆山市锦溪人民医院

出　　处：《实用肝脏病杂志》2016年第6期657-662,共6页Journal of Practical Hepatology

基　　金：国家973课题(编号:2012CB517501);国家自然科学基金资助项目(编号:81270491/81470840);上海市科委重点项目(编号:10411956300);上海市卫生系统优秀学科带头人计划(编号:XBR2011007)

摘　　要：目的通过血清脂质组学分析,研究CHB患者脂质代谢特征。方法在健康人(n=23)和肝活检证实的CHB患者(n=17),采用超高效液相色谱-串联质谱(UPLC-MS/MS)测定血清脂质组学代谢产物;构建正交偏最小二乘判别分析(OPLS-DA)模型,结合单因素分析筛选差异脂质。结果 CHB组与健康人脂质代谢轮廓有显著性差异[OPLS-DA:R2=0.775,Q2=0.518,P(CV-ANOVA)=2.81×10-4],筛选出64种显著改变的脂质(VIP>1,P<0.05)。其中包括游离脂肪酸(FFA)、二酰甘油(DAG)、三酰甘油(TAG)、胆固醇酯(CE)、神经酰胺(Cer)、鞘磷脂(SM)、磷脂酰胆碱(PC)、磷脂酰肌醇(PI)、溶血磷脂酰胆碱(LPC)、缩醛磷脂酰乙醇胺(Pls Etn)等;CHB组DAG、CE、LPC、PlsE tn、Cer显著降低(均值较健康人降低百分比分别为18%、17%、10%、32%和29%,P<0.05);TAG中含高碳原子数目、多不饱和键脂肪酸的TAG降低(P<0.05);饱和以及单不饱和键的PC升高,含多不饱和键的PC下降(P<0.05);CHB组游离单不饱和脂肪酸(F-MUFA)较健康人升高36%(P<0.05),且与METAVIR肝组织炎症活动和纤维化评分呈正相关(Spearman相关性分析:活动性r=0.527,P<0.05,纤维化r=0.540,P<0.05)。结论 CHB患者脂质代谢与正常人有显著差异,脂质组学分析可能为评价肝脏炎症活动和纤维化程度提供无创诊断依据。Objective The aim of this study was to investigate serum lipid profiling of patients with chronic hepatitis B （CHB）. Methods A ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS） platform was applied for serum lipid profiling in 17 patients with CHB and 23 healthy volunteers. Orthogonal partial least squares discriminant analysis （OPLS-DA） model and univariate analysis were established to analyze the characteristic metabolites and the association with histological severities. Results There were significant lipids changes in the CHB patients [OPLS-DA：R2=0.775,Q2=0.518,P （CV-ANOVA）=2.81＆#237;10-4], and 64 lipids with significant differences （VIP〉1,P〈0.05） between the two groups were found;These lipids belonged to categories of free fatty acid （FFA）,triglyceride（TAG）,diglyceride（DAG）,cholesterol ester （CE）, ceramide（Cer）,sphingomyelin （SM）,phosphatidylcholine （PC）,phosphatidylinositol （PI）,lysophosphatidylcholine （LPC）,ethanolamine plasmalogen （PlsEtn）;There were lower levels of CE,DAG,Cer,LPC,PlsEtn in CHB （decreased by 18%,17%,10%,32% and 29%,P〈0.05）;TAG with higher carbon numbers and double bonds significantly decreased （P〈0.05）;PC with lower double bonds significantly increased and PC with higher double bonds decreased （P〈0.05）;The free monounsaturated fatty acids increased in CHB （increased by 36%,P〈0.05） and were positively correlated with the METAVIR inflammation and fibrosis scores （Spearman correlation r=0.527,P〈0.05 in activity,r=0.540,P〈0.05 in fibrosis）. Conclusion The patients with CHB have numerous changes in lipid metabolism,and the lipidomic profiling may provide possible non-invasive method for the evaluation of hepatic injuries in patients with CHB.

关 键 词：慢性乙型肝炎 脂质组学 超高效液相色谱 串联质谱 

分 类 号：R512.62[医药卫生—内科学]