Volatile anesthetics improve postischemic cardiac function and reduce infarction even when administered for only a brief time at the onset of reperfusion. A recent study showed that sevoflurane postconditioning (SPC) attenuated myocardial reperfusion injury, but the underlying mechanisms remain unclear. In this study, we examined the effects of sevoflurane on nitric oxide (NO) release and autophagic flux during the myocardial ischemia/reperfusion (I/R) injury in rats in vivo and ex vivo. Male rats were subjected to 30 min ischemia and 2 h reperfusion in the presence or absence of sevoflurane (1.0 minimum alveolar concentration) during the first 15 min of reperfusion. We found that SPC significantly improved hemodynamic performance after reperfusion, alleviated postischemic myocardial infarction, reduced nicotinamide adenine dinucleotide content loss, and cytochrome c release in heart tissues. Furthermore, SPC significantly increased the phosphorylation of endothelial nitric oxide synthase (NOS) and neuronal nitric oxide synthase, and elevated myocardial NOS activity and NO production. All these effects were abolished by treatment with an NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v.). We also observed myocardial I/R-induced accumulation of autophagosomes in heart tissues, as evidenced by increased ratios of microtubule-associated protein 1 light chain 3 II/I, up-regulation of Beclin 1 and P62, and reduced lysosome-associated membrane protein-2 expression. SPC significantly attenuated I/R-impaired autophagic flux, which were blocked by L-NAME. Moreover, pretreatment with the autophagic flux blocker chloroquine (10 mg/kg, i.p.) increased autophagosome accumulation in SPC-treated heart following I/R and blocked SPC-induced cardioprotection. The same results were also observed in a rat model of myocardial I/R injury ex vivo, suggesting that SPC protects rat hearts against myocardial reperfusion injury by restoring I/R-impaired autophagic flux via an NO-dependent mechanism.

中文翻译：

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七氟醚后处理可通过NO依赖性机制恢复自噬通量，从而防止心肌缺血/再灌注损伤。

挥发性麻醉药即使在再灌注开始时仅短时间给药，也能改善缺血后的心脏功能并减少梗塞。最近的一项研究表明，七氟醚后处理（SPC）减轻了心肌再灌注损伤，但其潜在机制仍不清楚。在这项研究中，我们研究了体内和离体大鼠体内七氟醚对一氧化氮（NO）释放和自噬通量在大鼠心肌缺血/再灌注（I / R）损伤中的作用。在再灌注的前15分钟内，在有或没有七氟醚（最低肺泡浓度为1.0）下，对雄性大鼠进行30分钟的局部缺血和2小时的再灌注。我们发现SPC可显着改善再灌注后的血液动力学性能，减轻缺血后心肌梗塞，减少烟酰胺腺嘌呤二核苷酸含量的损失，并减少心脏组织中细胞色素c的释放。此外，SPC显着增加了内皮一氧化氮合酶（NOS）和神经元一氧化氮合酶的磷酸化，并增加了心肌NOS的活性和NO的产生。通过使用NOS抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，10 mg / kg，静脉注射）治疗，所有这些作用均被消除。我们还观察到心肌I / R诱导的自噬体在心脏组织中的蓄积，如微管相关蛋白1轻链3 II / I的比例增加，Beclin 1和P62的上调以及溶酶体相关膜蛋白减少所证明的那样。 -2表达式。SPC显着减弱了I / R损伤的自噬通量，该通量被L-NAME阻断。而且，自噬通量阻滞剂氯喹（10 mg / kg，腹膜内）预处理在I / R后增加了SPC处理的心脏中自噬体的蓄积，并阻断了SPC诱导的心脏保护作用。在离体心肌I / R损伤的大鼠模型中也观察到了相同的结果，这表明SPC通过通过NO依赖性机制恢复I / R受损的自噬通量来保护大鼠心脏免受心肌再灌注损伤。