Our previous study shows that nicotinamide adenine dinucleotide phosphate (NADPH) plays an important role in protecting against cerebral ischemia injury. In this study we investigated whether NADPH exerted cardioprotection against myocardial ischemia/reperfusion (I/R) injury. To induce myocardial I/R injury, rats were subjected to ligation of the left anterior descending branch of coronary artery for 30 min followed by reperfusion for 2 h. At the onset of reperfusion, NADPH (4, 8, 16 mg· kg⁻¹· d⁻¹, iv) was administered to the rats. We found that NADPH concentrations in plasma and heart were significantly increased at 4 h after intravenous administration. Exogenous NADPH (8−16 mg/kg) significantly decreased myocardial infarct size and reduced serum levels of lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I). Exogenous NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and caspase-3. In addition, exogenous NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. We conducted in vitro experiments in neonatal rat cardiomyocytes (NRCM) subjected to oxygen–glucose deprivation/restoration (OGD/R). Pretreatment with NADPH (60, 500 nM) significantly rescued the cell viability and inhibited OGD/R-induced apoptosis. Pretreatment with NADPH significantly increased the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in OGD/R-treated NRCM. Compound C, an AMPK inhibitor, abolished NADPH-induced AMPK phosphorylation and cardioprotection in OGD/R-treated NRCM. In conclusion, exogenous NADPH exerts cardioprotection against myocardial I/R injury through the activation of AMPK/mTOR pathway and inhibiting mitochondrial damage and cardiomyocyte apoptosis. NADPH may be a potential candidate for the prevention and treatment of myocardial ischemic diseases.

我们以前的研究表明，烟酰胺腺嘌呤二核苷酸磷酸（NADPH）在预防脑缺血损伤中起着重要作用。在这项研究中，我们调查了NADPH是否对心肌缺血/再灌注（I / R）损伤发挥了心脏保护作用。为了诱发心肌I / R损伤，将大鼠的冠状动脉左前降支结扎30分钟，然后再灌注2 h。再灌注开始时，NADPH（4，8，16 mg·kg ^-1 ·d ^-1，iv）给予大鼠。我们发现静脉内给药后4小时血浆和心脏中的NADPH浓度显着增加。外源NADPH（8-16 mg / kg）显着降低了心肌梗死面积，并降低了血清乳酸脱氢酶（LDH）和心肌肌钙蛋白I（cTn-1）的水平。外源NADPH明显降低了心肌细胞的凋亡率，并减少了PARP和caspase-3的裂解。此外，外源NADPH减少线粒体空泡，增加线粒体膜蛋白COXIV和TOM20，减少BNIP3L，增加Bcl-2，以保护线粒体功能。我们在遭受氧-葡萄糖剥夺/恢复（OGD / R）的新生大鼠心肌细胞（NRCM）中进行了体外实验。用NADPH预处理（60，500 nM）可显着挽救细胞活力并抑制OGD / R诱导的细胞凋亡。在OGD / R处理的NRCM中，NADPH预处理显着增加了AMPK的磷酸化，并下调了mTOR的磷酸化。化合物C（一种AMPK抑制剂）取消了NADPH诱导的OGD / R处理的NRCM中的AMPK磷酸化和心脏保护作用。总之，外源性NADPH通过激活AMPK / mTOR途径并抑制线粒体损伤和心肌细胞凋亡而对心肌I / R损伤发挥心脏保护作用。NADPH可能是预防和治疗心肌缺血性疾病的潜在候选药物。AMPK抑制剂可消除NADPH诱导的OGD / R处理的NRCM中的AMPK磷酸化和心脏保护作用。总之，外源性NADPH通过激活AMPK / mTOR途径并抑制线粒体损伤和心肌细胞凋亡而对心肌I / R损伤发挥心脏保护作用。NADPH可能是预防和治疗心肌缺血性疾病的潜在候选药物。AMPK抑制剂可消除NADPH诱导的OGD / R处理的NRCM中的AMPK磷酸化和心脏保护作用。总之，外源性NADPH通过激活AMPK / mTOR途径并抑制线粒体损伤和心肌细胞凋亡而对心肌I / R损伤发挥心脏保护作用。NADPH可能是预防和治疗心肌缺血性疾病的潜在候选药物。