摘要
Themainpathophysiologyofcerebralischemiaisthestructuralalterationintheneurovascularunit,coincidingwithneurovascularmatrixdegradation.Resveratrolhasbeenreportedtobeoneofthemostpotentchemopreventiveagentsthatcaninhibitcellularprocessesassociatedwithischemicstroke.Matrixmetalloproteinases(MMPs)hasbeenconsideredasapotentialdrugtargetforthetreatmentofcerebralischemia.Toexplorethis,wetriedtoinvestigatetheinteractionofresveratrolwithMMPsthroughmoleculardockingstudies.At30minutesbeforeand2hoursaftercerebralischemia/reperfusioninducedbyocclusionofthemiddlecerebralartery,40mg/kgresveratrolwasintraperitoneallyadministered.Afterresveratroladministration,neurologicalfunctionandbrainedemaweresignificantlyalleviated,cerebralinfarctvolumewassignificantlyreduced,andnitriteandmalondialdehydelevelsinthecorticalandstriatalregionsweresignificantlydecreased.ThemoleculardockingstudyofresveratrolandMMPsrevealedthatresveratroloccupiedtheactivesiteofMMP-2andMMP-9.Thebindingenergyofthecomplexeswas–37.848672kJ/moland–36.6345kJ/molforMMP-2andMMP-9,respectively.IncaseofMMP-2,Leu164,Ala165andThr227wereengagedinH-BondingwithresveratrolandincaseofMMP-9,H-bondingwasfoundwithGlu402,Ala417andArg424residues.ThesefindingscollectivelyrevealthatresveratrolexhibitsneuroprotectiveeffectsoncerebralischemiathroughinhibitingMMP-2andMMP-9activity.
出版日期
2015年04月14日（中国期刊网平台首次上网日期，不代表论文的发表时间）
