Abstract
In myocardial ischemia‑reperfusion injury (MIRI), increased activity of the c‑Jun N‑terminal kinase (JNK) pathway and the activation of platelets that leads to the formation of platelet‑leukocyte aggregates (PLAs) have been observed. It was hypothesized that ischemic postconditioning in MIRI exerts cardioprotective effects by altering JNK activity, which in turn leads to reduced PLA levels. A total of 60 rats were randomly divided into 6 groups (n=10 for each group): i)Control; ii)ischemia‑reperfusion injury alone; iii)ischemia‑reperfusion with postconditioning (PostC group), iv)treatment with the JNK inhibitor‑SP600125; v)postC and treatment with anisomycin; and vi)treatment with the JNK activator‑anisomycin. Subsequently, the levels of PLA, infarct size, myocardial injury markers (creatinine kinase‑muscle/brain and troponin I) and were measured. Western blotting was used to determine the protein expression of phosphorylated‑JNK. MIRI led to increased myocardial infarct size that was associated with raised troponin I and creatine kinase‑muscle/brain. At different time points of MIRI, the level of PLA gradually increased. Compared with the injury‑reperfusion group, the level of PLA in the PostC and Inhibitor‑JNK groups was significantly reduced at 60min and 3h following reperfusion. MIRI was able to increase the expression of phosphorylated JNK. These effects were significantly reduced by ischemic postC or by treatment with SP600125. By contrast, the addition of anisomycin attenuated these protective effects. JNK is a critical mediator of MIRI. Ischemic postC can reduce the level of PLA during reperfusion by inhibiting the phosphorylation of JNK MAPK, thereby reducing MIRI. Pharmacological inhibition and activation of JNK can improve and reduce cardioprotective effects, respectively. These results explained the mechanism of the cardioprotection of postC and provided novel insight and target for the therapeutic strategy of MIRI.
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