A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial isc...A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.展开更多
目的探讨桂枝甘草汤提取物组分对心肌缺血再灌注心律失常的作用。方法结扎大鼠冠状动脉左前降支15 m in再灌注1 h,监测心电变化,并检测心肌组织ATP酶活性及NO含量。结果桂枝甘草汤提取物水组分、30醇组分有对抗心肌缺血再灌注损伤所致...目的探讨桂枝甘草汤提取物组分对心肌缺血再灌注心律失常的作用。方法结扎大鼠冠状动脉左前降支15 m in再灌注1 h,监测心电变化,并检测心肌组织ATP酶活性及NO含量。结果桂枝甘草汤提取物水组分、30醇组分有对抗心肌缺血再灌注损伤所致心律失常的作用,并且可提高大鼠心肌组织ATP酶活性和NO含量,与模型组比较有显著差异(P<0.05或P<0.01)。结论桂枝甘草汤有效组分可能是通过提高ATP酶的活性、增加NO的含量减轻缺血再灌注对心肌的损伤。展开更多
文摘A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.
文摘目的探讨桂枝甘草汤提取物组分对心肌缺血再灌注心律失常的作用。方法结扎大鼠冠状动脉左前降支15 m in再灌注1 h,监测心电变化,并检测心肌组织ATP酶活性及NO含量。结果桂枝甘草汤提取物水组分、30醇组分有对抗心肌缺血再灌注损伤所致心律失常的作用,并且可提高大鼠心肌组织ATP酶活性和NO含量,与模型组比较有显著差异(P<0.05或P<0.01)。结论桂枝甘草汤有效组分可能是通过提高ATP酶的活性、增加NO的含量减轻缺血再灌注对心肌的损伤。
