Postconditioning inhibits myocardial apoptosis during prolonged reperfusion via a JAK2-STAT3-Bcl-2 pathway

Background: postconditioning (postc) inhibits myocardial apoptosis after ischemia-reperfusion (i/r) injury. the jak2-stat3 pathway has anti-apoptotic effects and plays an essential role in the late protection of preconditioning. our aim was to investigate the anti-apoptotic effect of postc after prolonged reperfusion and the role of the jak2-stat3 pathway in the anti-apoptotic effect of postc. methods. wistar rats were subjected to 30 minutes ischemia and 2 or 24 hours (h) reperfusion,with or without postc (three cycles of 10 seconds reperfusion and 10 seconds reocclusion at the onset of reperfusion). separate groups of rats were treated with a jak2 inhibitor (ag490) or a pi3k inhibitor (wortmannin) 5 minutes before postc. immunohistochemistry was used to analyze bcl-2 protein levels after reperfusion. mrna levels of bcl-2 were detected by qrt-pcr. ttc staining was used to detect myocardial infarction size. myocardial apoptosis was evaluated by tunel staining. western-blot was used to detect p-stat3 and p-akt levels after reperfusion. results: there was more myocardial apoptosis at 24 h vs 2 h after reperfusion in all groups. postc significantly reduced myocardial apoptosis and elevated bcl-2 levels at both 2 and 24 hours after reperfusion. postc increased p-stat3 and p-akt levels after reperfusion. administration of ag490 reduced p-stat3 and p-akt levels and attenuated the anti-apoptotic effect of postc. wortmannin also reduced p-akt levels and attenuated the anti-apoptotic effect of postc but had no effect on p-stat3 levels. ag490 abrogated the up-regulation of bcl-2 by postc. conclusion: postc may reduce myocardial apoptosis during prolonged reperfusion via a jak2-stat3-bcl-2 pathway. as a downstream target of jak2 signaling,activation of pi3k/akt pathway may be necessary in the protection of postc. © 2011 tian et al; licensee biomed central ltd.