微囊藻毒素MC-LR影响小鼠脂质代谢的生物组学机理研究的开题报告.docx

微囊藻毒素MC-LR影响小鼠脂质代谢的生物组学机理研究的开题报告
一、选题背景
蓝藻是立足于淡、咸水环境中的一类原生生物，但长期以来它们的代表性成员----微囊藻已经呈现出了一系列的“意外”表现。微囊藻毒素可以对食物链中的各类生物（包括鱼、虾、牛、羊、鸟等）造成不同程度以上的久远性过敏和脏器损害，而且影响人们的健康。据不完全的调查数据，全世界约68%的淡水机构体现出了制约性水质问题，其中绝大多数原因都与微囊藻毒素ERL范畴内的毒素有着极大的关联。据此，微囊藻毒素已经成为了当下生态环境管理的重点问题。
二、研究意义
Lipidmetabolismisessentialforenergystorage,structuralorganization,andcellularsignaling.Dysregulationofeachstepofthiscomplexprocesscancauseseveremetabolicdisorders.Asapotenthepatotoxin,microcystin-LR(MC-LR)hasbeenlinkedtolipidmetabolismdisordersinanimalsandhumans.However,theunderlyingmechanismsarestillpoorlyunderstood,whichmakesitdifficulttodevelopeffectivetherapeuticinterventions.
三、研究目的
ThepurposeofthisstudyistoinvestigatetheunderlyingmechanismsofMC-LRonlipidmetabolismandidentifypotentialmetabolictargetsfortherapeuticintervention.Specifically,wewilluseasystemsbiologyapproachtointegratetranscriptomics,metabolomics,andlipidomicsdatatoinvestigatetheregulatorynetworksofMC-LR-inducedlipidmetabolismdisorders.
四、研究内容
1.MC-LR-inducedlipidmetabolismdisordersinmice
WewilluseamousemodeltoinvestigatetheeffectsofMC-LRonlipidmetabolism.Aftera14-dayintraperitoneal(i.p.)injectionofMC-LR,themicewillbesacrificed,andtheirliverandserumsampleswillbecollectedforfurtheranalysis.
2.Transcriptomicanalysis
RNAwillbeextractedfromthelivertissue,andwholetranscriptomeanalysiswillbecarriedouttoanalyzedifferentiallyexpressedgenes(DEGs)inresponsetoMC-LRexposure.GeneOntology(GO)andKyotoEncyclopediaofGenesandGenomes(KEGG)pathwayanalysiswillbeperformedtoidentifysignificantlyenrichedbiologicalprocessesandsignalingpathways.
3.Metabolomicanalysis
LC-MS/MS-basedmetabolomicsanalysiswillbeusedtoidentifydifferentiallyexpressedmetabolites(DEMs)intheserumandliversamples.Theresultswillbeanalyzedusingmultivariatestatisticalanalyses,suchasprincipalcomponentanalysis(PCA)andpartialleastsquaresdiscriminantanalysis(PLS-DA).
4.Lipidomicanalysis
Lipidomicsanalysiswillbeusedtoidentifydifferentiallipids(DLs)intheserumandliversamples.Multi-dimensionalmassspectrometr