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GRP78mRNA在高脂喂养大鼠肝脏中的表达和意义的综述报告.docx

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GRP78mRNA在高脂喂养大鼠肝脏中的表达和意义的综述报告 Introduction: Inrecentyears,theprevalenceofobesityandrelatedmetabolicdisordershaveincreasedworldwide.Liverdiseasessuchasnon-alcoholicfattyliverdisease(NAFLD)areassociatedwithobesityandarebecomingoneoftheleadingcausesofliver-relatedmorbidityandmortality.Endoplasmicreticulum(ER)stressisasignificantpathologicalfactorinthepathogenesisofNAFLD.OneoftheimportantbiomarkersforERstressisGRP78,whichisamolecularchaperon.Inthisreview,weaimedtosummarizetheexpressionandsignificanceofGRP78mRNAintheliverofhigh-fat-fedrats. ExpressionofGRP78mRNAintheliverofhigh-fat-fedrats: SeveralstudieshavedemonstratedtheoverexpressionofGRP78mRNAintheliverofhigh-fat-fedratscomparedtocontrolratsfedwithnormalchow.AstudybyRutkowskietal.(2008)showedthattheexpressionofGRP78mRNAwasupregulatedby70%intheliverofhigh-fat-fedmice.Similarly,anotherstudybyHeetal.(2017)showedincreasedexpressionofGRP78mRNAintheliverofhigh-fat-fedratscomparedtoratsfedwithachowdiet.Thesefindingssuggestthathigh-fatfeedingleadstoincreasedERstressintheliver. SignificanceofGRP78mRNAintheliverofhigh-fat-fedrats: TheincreaseinexpressionofGRP78mRNAintheliverofhigh-fat-fedratsisassociatedwithseveralpathologicalchangesthatoccurintheliver.TheaccumulationoftriglyceridesandcholesterolinhepatocytesleadstoERstress,whichischaracterizedbytheaccumulationofunfoldedproteins,resultingintheactivationoftheunfoldedproteinresponse(UPR)pathway.TheactivationofUPRpathwayresultsintheupregulationofGRP78mRNA,whichisanimportantcomponentoftheUPRresponse.However,prolongedERstressandUPRactivationcanleadtoapoptosisofhepatocytesandinflammation,whichcontributetoNAFLDprogression. SeveralstudieshavedemonstratedthetherapeuticpotentialoftargetingERstressandGRP78inNAFLD.AstudybyJiangetal.(2017)showedthattreatmentwiththenaturalcompoundcurcuminresultedindecreasedexpressionofGRP78mRNAandreducedendoplasmicreticulumstressintheliverofhigh-fat-fedmice.Similarly,anotherstudybyLuoetal.(2019)showedthatanovelcompound,CKD-516,whichtargetsGRP78,attenuated