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Investigation Of Relationship Between Cardioprotective Effects Of Diazoxide Postconditioning On Myocardial Ischemia/reperfusion Injury In Rats And Mitochondrial Permeability Transition Pore

Posted on:2009-10-25Degree:MasterType:Thesis
Country:ChinaCandidate:C T WuFull Text:PDF
GTID:2144360245977676Subject:Cardiovascular medicine
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Objective: Myocardial ischemia reperfusion injury model rats in vivo were prepared. The present study was aimed to explore the cardioprotective effects of diazoxide(mitoKATP opener) postconditioning on myocardial ischemia reperfusion injury. Furthermore,this study was to investigate the relationship between diazoxide postconditioning and mPTP by means of the intervention of cyclosporin A(mPTP opener) and atractyloside(mPTP inhibitor).Methodes: healthy SD rats models of myocardial ischemia reperfusion injury was established according to coronary artery ligation. Rats were randomly divided into 6 groups(n=12): sham operation group(Sham group), ischemia reperfusion injury group(IRI group), ischemic postconditioning group(Post group), diazoxide postconditioning group(Dz group), diazoxide postconditioning + atractyloside group(Dz+ATR group), diazoxide postconditioning + cyclosporin A group(Dz+ CsA group).Six rats in each group were randomly killed at reperfusion 10 minutes or 120 minutes. At the moment of reperfusion 10 minutes, the degree of mPT of ischemic myocardium was detected by ultraviolet spectrophotometry. At the moment of reperfusion 120 minutes, venous blood was sent to measure the concent of CK and CK-MB, myocardial infarction area was measured by TTC staining method, apoptotic cardiomyocytes were detected by in situ end labeling technique (TUNEL).and The severity of MIRI was measured by concent of CK,CK-MB in blood serum, apoptotic cardiomyocytes were detected by in situ end labeling technique(TUNEL), myocardial ultramicrostructures were detected by electro-microscopic visualization. Results: 1.Compared with sham-operation group, IRI,Post and Dz group induced obviously increasing in myocardial creatase level,, myocardial infarction area, Flameng average score and apoptosis index(AI). 2. Compared with IRI group, Post group and Dz group could significantly decreased myocardial creatase level, myocardial infarct area, Flameng average score and apoptosis index, but with no statistical differences between them. 3. Compared with IRI and Dz+ATR group, Dz+CsA group and Dz group could significantly decreased myocardial creatase level, Flameng average score and apoptosis index; compared with IRI group, Dz+ATR group could significantly decreased myocardial creatase level, Flameng average score and apoptosis index. 4. Compared with IRI and Dz+ATR group, Dz+CsA group and Dz group could significantly decreasedâ–³OD/ min; compared with Dz group, Dz+CsA group could significantly decreasedâ–³OD/ min; but with no statistical differences between IRI and Dz+ATR group.Conclusions: Both ischemic postconditioing and diazoxide postconditioning could decrease myocardial creatase level and myocardial infarction area, restrain apoptosis, alleviate myocardial ischemia reperfusion-injury in model rats in vivo;The close of mPTP played a protective role in diazoxide postconditioning;Possibly,the open of mitoKATP channels alleviated myocardial ischemia reperfusion-injury relation to mPTP, and relation to certain mechanism irrelevant to mPTP; these drugs could be a potential therapeutic agent for protecting heart subjected MIRI from synthetic pharmacologic actions including mPTP inhibitor and mitoKATP opener.
Keywords/Search Tags:myocardial ischemic-reperfusion injury, diazoxide postconditioning, mitochondrial ATP-sensitive potassium channel, mitochondrial permeability transition pore, apoptosis
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