Effects Of Ischemic Postconditioning And ATP Postconditioning On Myocardial Ischemia Reperfusion Injury

Objective To investigate the effects of ischemic postconditioning (IPO), adenosine triphosphate (ATP) and adenosine receptor agonist CGS-21680 and antagonist SCH58261 pharmacological postconditioning on myocardial ischemia reperfusion injury (MIRI), and to explore the mechanism.Methods Sixty New Zealand white rabbits were randomly divided into five groups (n=12 each):I/R group, IPO group, ATP group, CGS-21680 group and SCH58261+IPO group (SCH58261 group).The model of myocardial I/R was established. Malondialdaldehyde (MDA) and superoxide dismutase (SOD) in the five groups were evaluated at the end of 3h reperfusion. Ischemic and infarct areas were measured by Evans blue and NBT staining. The light microscope was used to observe the tissue changes of myocardium. Apoptosis was identified and quantified as apoptosis index (AI) using TUNEL method. The mRNA expression of caspase-3 and Bcl-2 in myocardial tissue was determined by real-time quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR).Results Compared with those in I/R group and SCH58261 group, myocardial infarct size and the level of MDA markedly decreased in IPO group, in ATP group and CGS-21680 group (P<0.05). The levels of SOD increased significantly (P<0.01). TUNEL method showed that AI significantly decreased and the histopathological changes of the myocardium were relieved obviously in IPO group, in ATP group and CGS-21680 group compared with those in IR group and SCH58261 group (P<0.01). The results of real-time RT-PCR showed that the mRNA expression of caspase-3 was down-regulated, while Bcl-2 was up-regulated in IPO group, in ATP and CGS-21680 group (P<0.01).No significant difference was observed between I/R group and SCH58261 group, and among the three groups of IPO group, ATP group and CGS-21680 group (P>0.05).Conclusion Ischemic postconditioning and ATP postconditioning attenuate the myocardial IR injury via activation of adenosine A2a receptor. The mechanism may be associated with the up-regulation of Bcl-2 mRNA expression and the down-regulation of caspase-3 expression, which inhibits oxidation stress and decreases cell apoptosis.