Spermine ameliorates ischemia/reperfusion injury in cardiomyocytes via regulation of autophagy.

Myocardial infarction could result in high morbidity and mortality and heart diseases of children have becoming prevalent. Functions of spermine administration on cardiomyocytes remain unknown. The present study was designed to investigate the role of spermine pretreatment on myocardial ischemia/reperfusion injury (IRI). A cell model of simulated ischemia/reperfusion injury was established by incubating neonatal Sprague-Dawley rat cardiomyocytes in ischemia medium and re-cultured in normal medium. Of note, spermine pretreatment significantly reduced apoptosis and increased viability of immature cardiomyocytes. Spermine pretreatment enhanced autophagic flux as determined by confocal microscopy and transmission electron microscopy. Furthermore, proteins of mammalian target of rapamycin (mTOR) pathway were significantly reduced in response to spermine pretreatment during IRI, while proteins related to autophagy were up-regulated. The cell viability was enhanced and apoptosis decreased by rapamycin after spermine pretreatment, while these were reversed by 3-methyladenine. However, when immature cardiomyocytes were pretreated with rapamycin or 3-methyladenine, followed by IRI and spermine administration, no significant changes of viability and apoptosis were observed. In conclusion, this study suggests that spermine is a potential novel approach for preventing IRI, especially in children.