Liraglutideprotectsagainstfocalcerebralischemicinjurywithdiabetesmellitusbyactivatingperoxisomeproliferator-activatedreceptors

Abstract:

Objective：Toobservetheeffectofliraglutideontheexpressionofperoxisomeproliferator-activatedreceptors（PPARs）inthebraintissueofdiabeticratsaftercerebralischemicinjury，andtofurtherinvestigatetheeffectofliraglutideoncerebralischemicinjurywithdiabetesmellitusandthepossiblemechanism.Methods：Forty-eightadultmaleSprague-Dawleyratswererandomlydividedintofourgroups：sham-operatedgroup（Shamgroup），diabetescerebralischemiagroup（DCIgroup），liraglutide-pretreatmentDCIgroup（Lirgroup），andinsulin-pretreatmentDCIgroup（Insgroup），with12ratsineachgroup.Diabeteswasinducedbyintraperi－tonealinjectionofstreptozotocin，andamodelofpermanentmiddlecerebralarteryocclusion（MCAO）wasestablishedinthediabeticrats.TheratsintheLirgroupandInsgroupwereintraperitoneallyinjectedwithliraglutide（100μg/kg，q12h）andinsulin（2U/kg，q12h），respectively，7daysbeforeMCAO，whiletheothertwogroupswereinjectedwithanequalvolumeofnormalsalineduringthesameperiodoftime.Neurologicaldeficitscoresweredeterminedat24hoursafterMCAO.Thentheratsweredecapitated，andtheirbraintissuesweretakenouttomeasuretheinfarctareabyTTCstaining.WesternblottingwasusedtomeasuretheexpressionofPPARα，PPARβ，PPARγ，nuclearfactor-kappaBp65（NF-κBp65），andtumornecrosisfactor-α（TNF-α）intheischemicarea.Results：TheLirgroupandInsgroupshowedsignificantreductionsinbloodglucoseafterinjectionofliraglutideorin－sulin（P=0.000，P=0.000）.TheShamgroupshowednoneuro－logicaldeficit；comparedwiththeDCIgroup，theInsgrouphadnosignificantchangeinneurologicaldeficitscore，buttheLirgroupshowedasignificantreductioninneurologicaldeficitscore（P=0.00８）.TTCstainingshowedthatnoinfractwasobservedintheShamgroup；comparedwiththeDCIgroup，theInsgrouphadnosignificantchangeininfarctvolume，buttheLirgroupshowedasignificantreductionininfarctvolume（P=0.033）.WesternblotshowedsignificantdifferencesintheexpressionlevelsofPPARα，PPARβ，PPARγ，NF-κBp65，andTNF-αbetweentheShamgroup，theDCIgroup，theInsgroup，andtheLirgroup（F=15.826，P=0.000；F=21.988，P=0.000；F=21.132，P=0.000；F=21.023，P=0.000；F=63.607，P=0.000）；comparedwiththeDCIgroup，theInsgrouphadnosignificantchangesintheexpressionoftheaboveproteins，buttheLirgroupshowedsignificantincreasesintheexpressionofPPARα，PPARβ，andPPARγ（P=0.000，P=0.000，P=0.000）andsignificantreductionsintheexpressionofNF-κBp65andTNF-α（P=0.000，P=0.000）.Conclusion：Liraglutidehasacertainprotectiveeffectagainstfocalcerebralischemicinjuryindiabeticrats，possiblybyup-regulatingtheexpressionofPPARα，PPARβ，andPPARγanddown-regulatingtheexpressionofNF-κBp65andTNF-α.