Reperfusion therapy must be applied as soon as possible to attenuate the ischemic insult of acute myocardial infarction(AMI).However reperfusion is responsible for additional myocardial damage,which likely involves op...Reperfusion therapy must be applied as soon as possible to attenuate the ischemic insult of acute myocardial infarction(AMI).However reperfusion is responsible for additional myocardial damage,which likely involves opening of the mitochondrial permeability transition pore(mPTP).In reperfusion injury,mitochondrial damage is a determining factor in causing loss of cardiomyocyte function and viability.Major mechanisms of mitochondrial dysfunction include the long lasting opening of mPTPs and the oxidative stress resulting from formation of reactive oxygen species(ROS).Several signaling cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning,obtained with brief intermittent ischemia or with pharmacological agents.These pathways converge on a common target,the mitochondria,to preserve their function after ischemia/reperfusion.The present review discusses the role of mitochondria in cardioprotection,especially the involvement of adenosine triphosphate-dependent potassium channels,ROS signaling,and the mPTP.Ischemic postconditioning has emerged as a new way to target the mitochondria,and to drastically reduce lethal reperfusion injury.Several clinical studies using ischemic postconditioning during angioplasty now support its protective effects,and an interesting alternative is pharmacological postconditioning.In fact ischemic postconditioning and the mPTP desensitizer,cyclosporine A,have been shown to induce comparable protection in AMI patients.展开更多
目的探讨辛伐他汀预处理对缺血再灌注损伤的保护作用及其作用机制。方法结扎冠状动脉左前降支3h后再开放60min,在20只血脂正常兔建立缺血再灌注模型,随机分为对照组、辛伐他汀组、格列苯脲组和格列苯脲加辛伐他汀组。再灌注结束后,测定...目的探讨辛伐他汀预处理对缺血再灌注损伤的保护作用及其作用机制。方法结扎冠状动脉左前降支3h后再开放60min,在20只血脂正常兔建立缺血再灌注模型,随机分为对照组、辛伐他汀组、格列苯脲组和格列苯脲加辛伐他汀组。再灌注结束后,测定各组血清心肌型肌酸激酶同工酶(MB isoenzyme of creatine kinase,CK-MB)活性,用伊文蓝及氯化三苯四唑啉染色计算心肌梗死面积。结果辛伐他汀组心肌梗死面积及CK-MB活性较对照组和格列苯脲组减少(P<0.01),格列苯脲组与对照组差异无统计学意义(P>0.05),格列苯脲加辛伐他汀组较对照组减小(P<0.05),但仍明显高于辛伐他汀组(P<0.05)。结论辛伐他汀可明显减小缺血再灌注模型的心肌梗死面积,对缺血再灌注损伤具有保护作用,可能与辛伐他汀激活三磷腺苷敏感性钾通道有关。展开更多
基金Supported by National Institutes of Cardiovascular ResearchRegione Piemonte,PRIN,ex-60% and Compagnia di San Paolo,Italy
文摘Reperfusion therapy must be applied as soon as possible to attenuate the ischemic insult of acute myocardial infarction(AMI).However reperfusion is responsible for additional myocardial damage,which likely involves opening of the mitochondrial permeability transition pore(mPTP).In reperfusion injury,mitochondrial damage is a determining factor in causing loss of cardiomyocyte function and viability.Major mechanisms of mitochondrial dysfunction include the long lasting opening of mPTPs and the oxidative stress resulting from formation of reactive oxygen species(ROS).Several signaling cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning,obtained with brief intermittent ischemia or with pharmacological agents.These pathways converge on a common target,the mitochondria,to preserve their function after ischemia/reperfusion.The present review discusses the role of mitochondria in cardioprotection,especially the involvement of adenosine triphosphate-dependent potassium channels,ROS signaling,and the mPTP.Ischemic postconditioning has emerged as a new way to target the mitochondria,and to drastically reduce lethal reperfusion injury.Several clinical studies using ischemic postconditioning during angioplasty now support its protective effects,and an interesting alternative is pharmacological postconditioning.In fact ischemic postconditioning and the mPTP desensitizer,cyclosporine A,have been shown to induce comparable protection in AMI patients.
文摘目的探讨辛伐他汀预处理对缺血再灌注损伤的保护作用及其作用机制。方法结扎冠状动脉左前降支3h后再开放60min,在20只血脂正常兔建立缺血再灌注模型,随机分为对照组、辛伐他汀组、格列苯脲组和格列苯脲加辛伐他汀组。再灌注结束后,测定各组血清心肌型肌酸激酶同工酶(MB isoenzyme of creatine kinase,CK-MB)活性,用伊文蓝及氯化三苯四唑啉染色计算心肌梗死面积。结果辛伐他汀组心肌梗死面积及CK-MB活性较对照组和格列苯脲组减少(P<0.01),格列苯脲组与对照组差异无统计学意义(P>0.05),格列苯脲加辛伐他汀组较对照组减小(P<0.05),但仍明显高于辛伐他汀组(P<0.05)。结论辛伐他汀可明显减小缺血再灌注模型的心肌梗死面积,对缺血再灌注损伤具有保护作用,可能与辛伐他汀激活三磷腺苷敏感性钾通道有关。
