Objective To assess the role of mitochondrial permeability transition pore (MPTP) opening inhibition in cardioprotection by α7 nicotinic acetylcholine receptor (α7nAChR) agonist and limb remote ischemia postconditioning. Methods Sixty male Sprague-Dawley rats were randomly divided into four groups (n=15): Control group (C group), PNU282987 postconditioning group (P group), lime remote ischemia postconditioning group (L group), combined PNU282987 postconditioning and lime remote ischemia postconditioning group (P+L group). In each group, the left anterior descending coronary artery was ligated for 30 min followed by a 120 min reperfusion. In C group, no additional intervention was performed. In P group, α7nAChR agonist, PNU282987 (2.0 mg/kg), was injected intravenously immediately before a 120-min reperfusion. After 20 min of LAD ligation in L group, blood flow in the bilateral hind limbs was stopped for 10 min and then opened before reperfusion. In P+L group, rats received the same protocols as those of the L and P groups. The function of MPTP was assessed by mitochondrial calcium retention capacity (CRC) test. Real-time quantitative polymerase chain reaction (RQ-PCR) analysis and TUNEL apoptosis test were used to quantify the expression of genes associated with apoptosis and cardiomyocyte apoptotic index. Results Compared to C group, mitochondrial CRC in P, L, P+L groups were significantly increased. Compared to P and L groups, mitochondrial CRC in P+L group were significantly increased. The results of RQ-PCR showed that compared to C group, myocardial expression of Bcl-2 mRNA was significantly enhanced in P, L and P+L groups, while myocardial expression of Bax mRNA was significantly decreased in P, L and P+L groups. The TUNEL apoptosis test showed that cardiomyocyte apoptosis index was significantly decreased in P, L and P+L groups compared to C group. Conclusions Both α7nAChR agonist and limb remote ischemia postconditioning can decrease the cardiomyocyte apoptosis by suppressing MPTP opening. Combining two interventions can obtained enhances MPTP opening and cardiomyocyte apoptotic inhibitory effects.