Myocardial ischemia/reperfusion (I/R) injury is a major cause of mortality and morbidity worldwide. Among factors contributing to I/R injury,
proteolytic enzymes could also cause cellular injury, expand the injured area and induce
inflammation, which then lead to cardiac dysfunction. Therefore,
protease inhibition seems to provide therapeutic benefits. Previous studies showed the cardioprotective effect of
secretory leukocyte protease inhibitor (SLPI) against myocardial I/R injury. However, the effect of a post-ischemic treatment with SLPI in an in vivo I/R model has never been investigated. In the present study, recombinant human (rh) SLPI (rhSLPI) was systemically injected during coronary artery occlusion or at the onset of reperfusion. The results show that post-ischemic treatment with rhSLPI could significantly reduce
infarct size,
Lactate Dehydrogenase (LDH) and
Creatine kinase-MB (CK-MB) activity, inflammatory
cytokines and
protein carbonyl levels, as well as improving cardiac function. The cardioprotective effect of rhSLPI is associated with the attenuation of
p38 MAPK phosphorylation, Bax,
caspase-3 and -8
protein levels and enhancement of pro-survival
kinase Akt and ERK1/2 phosphorylation. In summary, this is the first report showing the cardioprotective effects against myocardial I/R injury of post-ischemic treatments with rhSLPI in vivo. Thus, these results suggest that SLPI could be used as a novel therapeutic strategy to reduce myocardial I/R injury.