乙型肝炎病毒感染者血清脂蛋白亚类及其组分的定量特征  

Quantitative characteristics of serum lipoprotein phenotypes for HBV patients

作　　者：易小璇 胡森林 孙阳 黄庆霞 唐惠儒[1,3] YI Xiaoxuan;HU Senlin;SUN Yang;HUANG Qingxia;TANG Huiru(School of Life Sciences,Human Phenome Institute,State Key Laboratory of Genetic Engineering,Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics,Shanghai 200438,China;Division of Cardiology,Department of Internal Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学生命科学学院,人类表型组研究院,遗传工程国家重点实验室,代谢组学与系统生物学实验室,上海200438 [2]华中科技大学同济医学院附属同济医院心血管内科,武汉430030 [3]复旦大学附属中山医院,上海200032

出　　处：《上海交通大学学报（医学版）》2023年第2期143-151,共9页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家重点研发计划(2021YFC2500600,2021YFC2500604,2022YFC3400700,2022YFA0806400);国家自然科学基金(31821002)

摘　　要：目的·既往研究发现乙型肝炎病毒(hepatitis B virus,HBV)感染会引起宿主脂蛋白改变,但脂蛋白亚类及其组分对HBV感染的应答规律未见报道。该研究拟通过定量分析HBV感染者的血清脂蛋白亚类及其组分,研究HBV感染引起的血清脂蛋白谱的变化特征。方法·纳入2017年3—6月就诊于华中科技大学同济医学院附属同济医院心内科的乙型肝炎病毒表面抗原阳性[HBsAg(+)]患者(n=40),同期纳入40例HBsAg阴性[HBsAg(-)]对照人群。使用核磁共振氢谱(proton nuclear magnetic resonance,1H-NMR)定量分析血清脂蛋白亚类及其组分,通过正交偏最小二乘判别分析、组间差异分析、逻辑回归分析和Spearman相关分析探索慢性HBV患者血清脂蛋白谱的变化规律。结果·HBsAg(+)组中大部分脂蛋白亚类及其组分水平显著低于HBsAg(-)组。校正年龄、性别、高血压、糖尿病以及心血管疾病因素后,总极低密度脂蛋白(very-lowdensitylipoprotein,VLDL)、VLDL1~VLDL3、中间密度脂蛋白(intermediate-densitylipoprotein,IDL)、小颗粒的高密度脂蛋白(small high-density lipoprotein 4,HDL4)和non-HDL及其组分依然是HBV感染的保护因素(OR<1,P<0.01),而VLDL5中的三酰甘油(triacylglycerol,TAG)占总脂质(total lipid,LP)的百分比[VLDL5-(TAG/LP)]则是HBV感染的危险因素(OR>1,P<0.01)。此外,HBsAg(+)人群的炎症程度与HDL4中的脂质组分水平高度负相关(r在-0.71~-0.51之间,P≤0.002)。通过特征筛选获得6个脂蛋白亚类指标,构建HBV感染诊断模型的AUC为0.861。结论·HBV感染影响肝脏分泌的脂蛋白的代谢转化,且脂蛋白亚类及其组分可用以区分HBV引起的表面抗原阳性患者。Objective·Previous studies showed that hepatitis B virus(HBV)infection caused outstanding changes in host lipoproteins.However,there are no reports on such component changes of lipoprotein subfractions.This study aimed to quantify the HBV-caused changes in the serum lipoprotein subfractions and their components.Methods·Hepatitis B surface antigen-positive[HBsAg(+)]patients at Division of Cardiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from March to June 2017 were included(n=40),and 40 HBsAg-negative[HBsAg(-)]population were matched as controls.Serum lipoprotein subfractions and their components were quantified by using 1H-NMR.Orthogonal partial least-squares discriminant analysis(OPLS-DA),variance analysis between the two groups,logistic regression analysis and Spearman correlation analysis were conducted to reveal the lipoprotein changes in chronic HBV patients against controls.Results·HBsAg(+)population had significantly lower levels in most lipoprotein subfractions than HBsAg(-)population.After adjustments for age,gender,hypertension,diabetes mellitus and coronary heart disease,the levels of total VLDL,VLDL1-VLDL3,IDL,HDL4,non-HDL and their components were protective factors for HBV infection(OR<1,P<0.01).In contrast,VLDL5-(TAG/LP)was a risk factor for HBV infection(OR>1,P<0.01).In addition,the severity of inflammation in the HBsAg(+)population was negatively correlated with the levels of lipids in HDL4 with correlation coefficient ranging from-0.71 to-0.51(P≤0.002).Six lipoprotein subfractions were obtained through feature screening,and the AUC of HBV infection diagnosis model was 0.861.Conclusion·HBV infection causes significant changes in liver-excretion of lipoproteins and their circulation metabolism;the lipoprotein phenotypes can differentiate HBV-infected patients from controls.

关 键 词：脂蛋白 1H-NMR 乙型肝炎病毒 慢性乙型肝炎 

分 类 号：R33.1[医药卫生—人体生理学]