Proteasome inhibitor MG-132 inhibits myocardial reperfusion injury in rats by suppressing expression of inflammatory factors

Objective To investigate the influence of proteasome inhibitor MG-132 on inflammatory factors in rat model of myocardial ischemia/reperfusion. Methods Adult Sprague-Dawley rats were divided into 4 groups. I/R group: left anterior descending (LAD) coronary artery was ligated for 30 min, and then reperfused for 0, 1, 2, 6, 24 h; I/R+T group: MG-132 was used for treatment, and other procedures as I/R group; Sham operation group; Sham operation+T group. At 5 min before reperfusion, MG-132 (0.75 mg/kg) was given intravenously in I/R+T group and Sham operation+T group, and normal saline for I/R group and sham operation group. The changes of myocardial ultrastructure were checked, and the protein and mRNA levels of NF-κBp65 and TNF-α, the number of PMN, the activity of MPO and survival of each group were detected. Results As compared with Sham operation group and Sham operation+T group, the protein and mRNA levels of NF-κBp65 and TNF-α, the number of polymorphonuclear leucocytes (PMN) and the activity of myeloperoxidase (MPO) were significantly increased in I/R group (P0.05), and these indexes were significantly higher at 1, 2, 6, 24 h after reperfusion than that at 0 h (P0.05). The cardiocytes diffused and swelled, the myofilament was lysed, and the mitochondria swelled and vacuolizated. The above-mentioned inflammatory factors of I/R+T group were significantly decreased as compared with I/R group (P0.05), and could keep at a low level at least for 24 h. The damaged degree of cardiocytes in I/R+T group was less and the mortality due to deadly arrhythmia was lower than that of I/R group. Conclusion Myocardial reperfusion injury can be inhibited by proteasome inhibitor MG-132 through suppressing the expression of inflammatory factor in rats.