Effect of morphine preconditioning on necroptosis during myocardial ischemia-reperfusion injury in rats with heart failure

Abstract

Objective \nTo evaluate the role of morphine preconditioning on necroptosis during myocardial ischemia-reperfusion (I/R) injury in the rats with heart failure. \n \n \nMethods \nClean-grade adult male Sprague-Dawley rats, weighing 200-230 g, were injected with 2 mg/kg doxorubicin via the tail vein once a week for 6 consecutive weeks to establish the chronic heart failure model.Thirty rats with chronic heart failure at the end of 8th week were divided into 3 groups (n=10 each) using a random number table method: sham operation group (group S), I/R group and morphine preconditioning group (group MPC). Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion in each group except group S. In group MPC, the rats were subjected to 3 cycles of 5-min infusion of 0.1 mg/kg morphine via the femoral vein at 5 min intervals before ischemia.The animals were sacrificed at the end of reperfusion, and the myocardial specimens were obtained for determination of the area at risk (AAR), infarct size (IS), expression of Fas mRNA (by quantitative real-time polymerase chain reaction) and expression of Fas, receptor-interacting protein 1 (RIP1) and RIP3 (by Western blot). The IS/AAR ratio was calculated. \n \n \nResults \nCompared with group S, the IS and IS/AAR ratio were significantly increased at the end of reperfusion, and the expression of Fas protein and mRNA, RIP1 and RIP3 was up-regulated in group I/R (P<0.05). Compared with group I/R, the IS and IS/AAR ratio were significantly decreased at the end of reperfusion, and the expression of Fas protein and mRNA, RIP1 and RIP3 was down-regulated in group MPC (P<0.05). \n \n \nConclusion \nThe mechanism by which morphine preconditioning reduces myocardial I/R injury is related to inhibiting necroptosis in the rats with heart failure. \n \n \nKey words: \nMorphine;\xa0Ischemic preconditioning;\xa0Heart failure;\xa0Myocardial reperfusion injury;\xa0Necrosis