代谢组学法评价紫苏子抗小鼠急性肝损伤的作用.docx

代谢组学法评价紫苏子抗小鼠急性肝损伤的作用耿芹1，郑床木2，管政2,3,*，张小红2，朱超2，杨曙明2，陈爱亮2,*（1.华烁科技股份有限公司，湖北武汉430074；2.中国农业科学院农业质量标准与检测技术研究所，北京100081；3.浙江中医药大学药物研究所，浙江杭州310053）摘要：用代谢组学法对紫苏子抗小鼠急性肝损伤作用进行评价。研究构建四氯化碳（CCl4）致小鼠急性肝损伤模型，采用流动注射-三重四极杆-飞行时间质谱联用系统对模型组、紫苏子给药组、阳性药联苯双酯给药组及正常对照组动物的肝组织及全血代谢轮廓谱进行比较。采用主成分分析法对各组数据进行分析并初步筛选潜在生物标志物。代谢组学分析、血生化指标检测及病理研究表明，20g/kg生药当量的紫苏子醇提物对CCl4致小鼠急性肝损伤模型具有与联苯双酯临床等效剂量相似的保肝作用。结果表明，柠檬酸、磷脂酸、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺等9个代谢物为CCl4致小鼠急性肝损伤及紫苏子保肝作用的潜在生物标志物；作用途径与脂质过氧化、能量代谢等有关。关键词：紫苏子；流动注射；质谱；急性肝损伤；代谢组学；主成分分析ProtectiveEffectofPerillaSeedonAcuteHepaticInjuryinMiceasEvaluatedbyMetabolomicAnalysisGENGQin1,ZHENGChuang-mu2,GUANZheng2,3,*,ZHANGXiao-hong2,ZHUChao2,YANGShu-ming2,CHENAi-liang2,*(1.HaisoTechnologyCo.Ltd.,Wuhan430074,China;2.InstituteofQualityStandardsandTestingTechnologyforAgro-products,ChineseAcademyofAgriculturalSciences,Beijing100081,China;3.InstituteofMateriaMedica,ZhejiangChineseMedicalUniversity,Hangzhou310053,China)Abstract:Theobjectiveofthisstudywastoevaluatetheprotectiveeffectofperilla(Perillafrutescens)seedonacutehepaticinjuryinducedbycarbontetrachloride.Identi?cationofpotentialbiomarkerswasperformedbyhigh-performanceliquidchromatography(HPLC)andflowinjectionelectrosprayionizationwithtime-of-flight(TOF)massspectrometry(FIMS)combinedwithprincipalcomponentanalysis(PCA).Bloodandhepatictissuemetabolicprofileswereacquiredandcorrelatedwiththebiochemicalandhistopathologicalresults.Inthiswork,metabolomicprofiling,andbiochemicalandhistopathologicalstudiestogethercon?rmedtheliverprotectiveeffectofperillaseed.Perillaseedatadoseequivalentto20g/kgperdaycausedasimilareffecttothatofbifendate(3.5mg/kgperday).Comparedwithnormalcontrolgroup,theexpressionofLysoPC,LysoPE,PA,carnitine,citricacid,inosine,methylatednucleoside,andtaurohyocholatewereincreasedsigni?cantlyinmodelgroup,whereastheoppositeresultswereobservedfortheanimalswhichhadgivenperillaseedextract.These?ndingsindicatedthatthedevelopedmetabonomicmethodbasedonFIMSmightbeusedasapotentiallypowerfultoolforfastandcomprehensiveestimationofthe