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1、Vascularprotectiveeffectofpretreatmentwithcandesartanoncerebralischemia-reperfusioninratsABSTRACTObjective:ToinvestigatethevascularprotectiveeffectofpretreatmentwithCandesartanonCerebralischemiainrats,weobservedthechangeandrelationshipbetweenendothelialnitricoxidesynthase(eNOS)andvascul
2、arendothelialgrowthfactor(VEGF)intheischemiapenumbra,withmiddlecerebralarteryocclusion(MCAO)byintraluminalsuturemethodinrats.Methods:72maleSDrats,12weeks,wererandomlydividedintoshamoperationgroup,ischemia-reperfusiongroup,candesartanlow-dosegroup[0.1mg/(kg.d)],andcandesartanhigh-dosegro
3、up[1mg/(kg.d)],therewere18ratsineachgroup,eachgroupwasrandomlydividedintotwosub-groups(n=9ineachgroup):reperfusion24hourand72hour.Normalsodiumwasdeliveredbyintragastricadministrationwith2ml/dinshamoperationgroupandischemia-reperfusiongroup,Candesartanwasdeliveredbyintragastricadministra
4、tionwith0.1mg/(kg.d)and1mg/(kg.d)incandesartanlow-dosegroup、candesartanhigh-dosegroup,respectively.Amodelofmiddlecerebralarteryocclusionwasinducedbyintraluminalsuturemethodafterfourweeksofdruggavage.Bloodpressurewasmeasuredpreoperatively.Cerebralbloodflowofischemicregionwasquantifiedbyl
5、aser-DopplerflowmetryafterMCAO.Neurologicalscoreswereperformedafter24and72hoursofreperfusion,thentheratsweredecapitatedandthebrainswereremoved.TheInfarctvolumewasmeasuredusingTTCstaining.Theexpressionofvascularendothelialgrowthfactorandendothelialnitricoxidesynthaseproteininischemicpenu
6、mbrawasdetectedbyImmunohistochemicalstainingandWesternblotanalysis.Results:(1)Inthesecondweekaftermedication,thebloodpressurewasdecreasedsignificantlyinthehigh-dosecandesartangroup,maintainingat85mmHg,andtherewasnosignificantantihypertensiveeffectinthelow-dosegroup.(2)Theneurological3sc
7、oresofthelow-doseandhigh-dosecandesartangroupsat24hourand72hourafterreperfusionweresignificantlybetterthanthoseoftheischemia-reperfusiongroup(P<0.05,respectively).(3)Infarctvolumeinlow-doseandhigh-dosecandesartangroupreducedto[(34±4)%,(30±3)%],thereisnosignificantdifferencebetw