Remote Liver Ischemic Preconditioning Attenuates Myocardial Ischemia/reperfusion Injury in Streptozotocin-induced Diabetic Rats
Abstract BACKGROUND: Diabetes mellitus (DM) exhibits a higher sensitivity to myocardial ischemia/reperfusion(I/R)injury and may compromise the effectiveness of cardioprotective interventions, including ischemic preconditioning. We previously found that liver ischemic preconditioning(RLIPC) could limit infarct size post I/R in normal rat hearts and further exerted anti-arrhythmic effects in diabetic or non-diabetic rats after myocardial I/R, however, little is known regarding the effect of RLIPC on infarct-sparing in diabetic hearts. In this study, we evaluated the protective effects of RLIPC on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats.METHODS:Type 1 diabetes mellitus was induced by one-time intraperitoneal injection of streptozotocin in Sprague–Dawley rats. Rats were exposed to 45 min of left anterior descendin(LAD) coronary artery occlusion, followed by 3 h of reperfusion. For liver ischemic preconditioning, four cycles of 5 min of liver I/R stimuli were performed before LAD occlusion. the cardioprotective effect of RLIPC was determined in diabetic rats.RESULTS: Compared to non-RLIPC treated DM rats, RLIPC treatment significantly reduced infarct size in diabetic hearts post I/R. RLIPC also improved cardiac functions including LVESP, LVEDP, dp/dtmax, and -dp/dtmax. In addition, RLIPC could largely preserved cardiac morphology by reducing the pathological score post I/R in diabetic hearts. Finally, western blotting analysis showed that RLIPC stimulated phosphorylation of ventricular GSK-3β and STAT-5, which are key components of RISK and SAFE signaling pathways.