超重人群中健康者与非酒精性脂肪性肝病患者的临床特征及血清脂质组学分析.docx
脂肪性肝病DOI：10.12449ZJCH240211超重人群中健康者与非酒精性脂肪性肝病患者的临床特征及血清脂质组学分析陈小燕，袁乙富，杜晟楠，曹勤，蒋元炸上海中医药大学附属普陀医院消化内科，上海200062留言储：蒋元炜,yuanyel014(ORQD:0000-0002-4979-4206)摘要：目的探究超重人群中，非酒精性脂肪性肝病(NAFLD)患者与健康人的临床指标与脂质代谢差异.方法本研究将体质副酸(BMl)>23kg/n?定义为超重人群，选取2020年8月2021年4月上海中医药大学附属普陀医院收治的62例超重NAFLD患者纳入超重NAFLD组，另选取同期超重健康体检者50例作为对照记录所有受试者的临床信息以及血液生化指标数据。应用超高效液相色谱-串联质谱法(UPLC-MS/MS)进行血清脂质组学分析；使用主成分分析法和正交偏最小二乘法判别分析对脂质组学数据进行多元统计分析。计数资料两组间比较采用2检验.计量资料两组间比较采用成组t检验或Wilcoxon秩和检验结果超重NAFLD组BMI显著高于超重对照组(Z=-Z365,P=O.018)血清学指标中,超重NAFLD组红细胞、血红蛋白、红细胞t咨、尿酸、总蛋白、球蛋白、ALP.GGTxALT、AST、月酶韩、彳氐密阂缠白、捌旦固酿甘油三酯、载脂蛋白B、血糖水平均显著高于超重对照组(尸值均<0.05).脂质组学分析结果显示两组间脂质代谢具有明显差异，共鉴定出差异性三质(VIP三>1,P<0.05)493个，其中超重NAFLD组中有143个月前显著上调,350个月孤显著下调。超重NAFLD组的平均脂肪酸总量是超重对照组的3.6倍.超重NAFLD组不饱和键数>3的甘油三酯含量较超重对照组降低(P<0.OO1),而不饱和键数3的甘油三酯含量较超重对照组增多(P<0.OOl).结论超重NAFLD患者的部分生化指标及脂质代谢产物明显异于超重健康人，血液内脂肪酸明显升高，甘油三酯中的含饱和脂肪链的种类显著升高。关键词：非酒精性脂肪性肝病；超重；体征和症状；脂质组学基金项目：上海市自然科学基金(22ZR1455900)；上海市卫健委临床研究专项面上项目(201940449);上海市普陀区卫生健康系统科技创新项目重点项目(ptkwws202201);上海中医药大学后备卓越中医人才项目(20D-RC-O2)；上海市名中医沈红权普陀传承工作室(ptzygzs2201,SHGZS-202224);每市普陀区杏林优青人才培养计划(ptxlyq2201)ClinicalfeaturesandserumIipidomicprofileofpatientswithnonalcoholicfattyliverdiseaseandhealthyindividualsintheoverweightpopulationCHENXiaoyan,YUANYifu,DUShengnan,CAOQinlJIANGYuanye.(DepartmentofGastroenterology,PutuoHospitaIAffiIiatedtoShanghaiUniversityofTraditionalChineseMedicine,Shanghai200062,China)Correspondingauthor:JIANGYuanye,yuanye1014)(ORCID:0000-0002-4979-4206)Abstract:OtyectiveToinvestigatethedifferencesinclinicalindicesandlipidmetabolismbetweenthepatientswithnonalcoholicfattyliverdisease(NAFLD)andhealthyindividualsintheoverweightpopulation.MethodsInthisstudy,bodymasshde×(BMI)>23kghzwasdefinedasoverweightAtotalof62overweightpatientswithNAFLDwhowereadmittedtoPutuoHospitalAffiliatedtoShanghaiUniversityofTraditionalChineseMedicinefromAugust2020toApril2021wereenrolledasOVefWeightNAFLDgroup,and50overweightindividualswhoUnderWerItphysicalexaminationduringthesameperiodoftimewereenrolledasCOntrDlgroup.Clinicalinformationandbloodbiochemicalparameterswererecordedforallsuects.Ultra-performanceliquidchromatography-tandemmassspectrometrywasusedtoanalyzeserumIipidomicprofile,andprincipalcomponentanalysisandorthogonalpartialleastsquares-disiminantanalysiswereusedtoperformthemultivariatestatisticalanalysisofIipidomicdata.Thechi-squaretestwasusedforcomparisonofcategoricaldatabetweentwogroups,andtheindependent-samplesftestorteWilcoxonrank-sumtestwasusedforcomparisonofcontinuousdatabetweentwogroups.ResultsTheoverweightNAFLDgrouphadasignificantlyhigherBMIthantheoverweightcontrolgroup(Z=-2365,P=0018).Asfbrserologicalmarkers,comparedwiththeoverweightcontrolgroupztheoverweightNAFLDgrouphadsignificantlyhigherlevelsofredbloodcells,hemoglobin,hematocrit,uricadd,totalprotein,globulin,alkalinephosphatase,gamma-glutamyltranspeptidase,alanineaminotransferase,aspartateaminotransferase,cholinesterase,low-densitylipoprotein,totalcholesterol,triglyceride,apolipoproteinB,andbloodglucose(all?<0.05),TheIipidomicanalysisshowedthattherewasasignificantdifferenceinlipidmetabolismbetweenthetwogroups,andatotalof493differentiallyexpressedlipidswereidentified(VIPvalue>l,P<0.05)lamongwhich143lipidsweresignificantlyUpregulatedand350lipidsweresignificantlydownregulatedintheoverweightNAFLDgroup.ThemeantotalfattyaddcontentintheoverweightNAnJDgroupwas3.6timesthatintheofweghtcontrolgroup.Comparedwiththeoverweightcontrolgroup,theoverweightNAFLDgrouphadasignificantreductioninthecontentOftriglyceridewrt>3unsaturatedbonds(尸<0.001)andasignificantineaseinthecontentOftriglyceridewith3unsaturatedbonds(P<0.001).COndUSiOnComparedwithhealthyoverweightindividuals,overweightNAFLDpatientstendtohavesignificantabnormalitiesinsomebiochemicalparametersandlipidmetabolites,withsignificantincreasesinthententoffattyacidinbloodandthetypesofsaturatedfatchainsintriglycerides.Keywords:Non-AlcoholicFattyLiverDisease;Overweight;SignsandSymptoms;LipidomicsResearchfunding:ShanghaiNaturalScienceFoundation(22ZR1455900);ShanghaiHealthandFamilyPlanningCommissionGinkalResearchProject(201940449);ShanghaiPutDistrictHealthSystemScienceandTechnologyInnovationPnDject(ptkwws202201);ShanghaiUniversityofTradrtionalChineseMedicineReserveOutstandingTraditionalChineseMedicineTalentsProject(20D-RC-02);ShanghaiFamousTraditionalChineseMedicinePutuoInheritanceStudio(ptzygzs2201,SHGZS-202224);ShanghaiPutuoDistrictXinglinExcellentYouthTalentTrainingProgram(ptxlyq2201)非酒精性脂肪性肝病（NAFLD）目前已成为一种常见的慢性肝病，被认为是一种以脂质储存和代谢紊乱为特征的疾病。NAFLD与肥胖密切相关，超过60%的月嶙人群患有NAFLD,而在非肥胖人群中，NAFLD的患病率则较低。研究表明，肥胖是NAFLD的独立危险因素,与正常体质量相比，肥胖导致NAFLD的发生风险增加3.5倍，体质量指数（BMl）与NAFLD风险之间存在明显的剂量依赖关系o此外，肥胖还会加速NAFLD的发展，使其更容易进展为肝纤维化、肝硬化和肝癌等严重肝病。肥胖和NAFLD之间的关系是相互作用的。肥胖患者往往伴随胰岛素抵抗和炎症反应，这些因素都可以促进NAFLD的发展而NAFLD患者中，脂肪酸（FA）释放增加，肝脏中的脂质代谢失调，以上因素也会进一步加重肥胖的发展（2）.但是，对于单纯超重的肥胖患者，其血糖、血压及血脂等代谢功能早期可能并无明显异常1310因此，超重NAFLD患者的临床特征及脂质代谢差异需进一步研究与探讨。脂质组学是代谢组学研究的一个新的分支，是指对生物样本中脂质分子进行系统性和全面性分析的一种技术。脂质不仅是人体中的能量供给和储存来源，也是构成细胞生物膜的成分，参与许多重要的代谢过程，脂质代谢途径的改变
