2型糖尿病对大鼠心肌缺血再灌注损伤救援激酶信号通路的影响.doc

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1、2型糖尿病对大鼠心肌缺血再灌注损伤救援激酶信号通路的影响【摘要】目的探讨2型糖尿病(T2DM)对心肌缺血后适应(ischemicpostconditioning，IPO)减轻心肌缺血再灌注损伤作用的影响及可能机制。方法高脂饮食联合STZ诱导制成T2DM大鼠模型，将60只雄性Wistar大鼠随机分为正常大鼠缺血再灌注组(A组)、正常大鼠缺血后适应组(B组)、糖尿病大鼠后适应组(C组)。3组均采用离体大鼠心脏Langendorff灌流方法，全心停灌30min，复灌60min，制成心肌缺血再灌注模型。B、C组在再灌注开始前先给予再灌注10s，全心停灌10s，共6次循环的IPO。免疫

2、组织化学染色及Western印迹法测定心肌磷酸化Akt，磷酸化糖原合成酶激酶(GSK3β)的表达。结果正常离体大鼠心肌IPO干预后磷酸化Akt及GSK3β的表达增强;而对T2DM大鼠给予IPO处理后磷酸化Akt及GSK3β的表达无增强，去磷酸化GSK3β表达增强。结论IPO对正常大鼠离体心脏缺血再灌注损伤有明确的保护作用，而对T2DM大鼠心肌缺血再灌注损伤无保护作用;其机制可能与糖尿病状态下影响再灌注损伤救援激酶信号通路，导致GSK3β活性(去磷酸化水平)增高有关。【关键词】缺血后适应;糖尿病;缺血再灌注损伤;再灌注损伤救援激酶信号通路【Abstract】Objec

3、tiveToelucidatetheeffectsofischemicpostconditioning(IPO)onischemia/reperfusion(I/R)cardiacandtheroleofreperfusioninjurysalvagekinasepathwayintype2diabeticrats.MethodsThetype2diabeticratswereinducedbytheintravenousinjectionofstreptozotocinandhighcaloricdiet.SixtyWistarratswererandomlydevided

4、intoI/Rinnomalrats(A),IPOinnormalrats(B),IPOindiabeticrats(C)groups.RatsweregivenforLangendorffisolatedheartperfusionwith30minofglobeischemiaand60minofreperfusion,thenthemodelsofgroupAweremade.ButtheratheartsofgroupBandCweresubjectedto6cyclesof10minofglobeischemiaand10minofreperfusionasIPOd

5、uringtheearlyminutesofreperfusion.Phosphorylationofaktandgsk3βwereanalyzedbyWesternblotandimmunohistochemicalstaining.ResultsThephosphoaktandphosphogsk3βexpressionswereincreasedmarkedlyinBgroup.ButcomparedthoseinAgrouptherewasnodifferenceinCgroup.Thephosphoaktandphosphogsk3βexpressio

6、nsinCgroupweremorelessthanthoseinBgroup.ConclusionsIPOmaysignificantlyprotectmyocardiuminisolatednormalrathearts.Butindiabeticrats,theprotectionofIPOhasnoeffect,themechanismofthisphenominonmayberelatedtogsk3βintheconditionofdiabetic.　　【Keywords】Ischemicpostconditioning;Diabetic;Ischemic/re

7、perfusioninjury;RISKpathway5　糖尿病是冠心病主要危险因素，急性心肌梗死(AMI)合并糖尿病人群的死亡率也高于非糖尿病人群。2003年VintenJohansen实验室提出了应用心肌缺血后适应处理(ischemicpostconditioning，IPO)可减轻心肌缺血再灌注损伤，其可能的机制是IPO激活再灌注损伤救援激酶(reperfusioninjurysalvageKinase，RISK)通路〔1，4〕。但IPO对糖尿病心肌保护作用目前研究甚少，而且IPO对糖尿病心肌是