Liver X receptor agonist treatment reduced splanchnic ischemia and reperfusion injury

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: artery occlusion;    oxygen‐;    free radicals;    apoptosis;    adhesion molecules;   

DOI  :  10.1189/jlb.0609438

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

LXRisanothermemberofthesuperfamilyofnuclearhormonereceptorsthatheterodimerizeswithRXRandregulatestheintracellularlevelsofcholesterolthroughgeneinductionofenzymesandproteinsinvolvedinthecholesterolmetabolismandtransport.LXRligandsinhibitthegeneexpressionofproinflammatorymediatorsinimmunostimulatedmacrophages;invivostudieshaveshownthatactivationofLXRreducestheinflammatoryresponseinamurinemodelofcontactdermatitisandatherosclerosis.NoreportshaveaddressedaroleforLXRsinpathophysiologyofintestinalischemia.TheaimofthisstudywastoinvestigatetheeffectsofT0901317,apotentLXRligand,inamousemodelofSAOshock,whichwasinducedbyclampingthesuperiormesentericarteryandtheceliactrunk,resultinginatotalocclusionofthesearteriesfor30min.Afterthisperiodofocclusion,theclampswereremoved.Micewerekilledat60minafterreperfusion.ThisstudyprovidestheevidencethatT0901317,LXRagonist,modulates:thedevelopmentofSAOshock;theinfiltrationofthetissuewithPMNs;theexpressionofTNF‐αandIL‐1β;thenitrationoftyrosineresidues;NF‐κBexpression;theMAPKphosphorylation(ERK,JNK,andp38);FasL;apoptosis;BaxandBcl‐2expression;andthedegreeoftissueinjurycausedbySAOshock.OurresultsimplythatLXRagonistsmaybeusefulinthetherapyofinflammation...

【 授权许可】

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