Nuclear factor-κB signaling pathway and autophagy in inhaled sevoflurane-produced delayed myocardial protection in rats

Abstract

Objective To evaluate nuclear factor （NF）-kB signaling pathway and autophagy in inhaled sevoflurane-produced delayed myocardial protection in rats. Methods Ninety-six adult male Sprague-Dawley rats, weighing 270-350 g, were randomly assigned into 6 groups （ n = 16 each） ： sham operation group （group S）, isch- emia-reperfusion （I/R） group, sevoflurane group （SEVO group）, specific NF-kB inhibitor parthenolide （PTN） group, dimethyl sulfoxide （DMSO） group and PTN ＋ sevoflurane group （ PTN ＋ SEVO group）. The animals were anesthetized with intraperitoneal pentobarbital 50 mg/kg, intubated and mechanically ventilated. Myocardial I/R was induced by 30 min of occlusion of the left anterior descending branch of coronary artery followed by 2 h of reperfusion. In group I/RI 33% oxygen was inhaled for 2 h. In group SEVO, 2.5% sevoflurane was inhaled for 2 h. In groups PTN and DMSO, PTN 500 μg/kg and DMSO were administered intraperitoneally 15 min before oxy- gen inhalation respectively. In group PTN ＋ SEVO, PTN 500 ttg/kg was administered intaperitoneally 15 min be- fore exposure to sevoflurane. Myocardial I/R was induced 24 h after intraperitoneal administration. Eight animals in each group were sacrificed immediately before ischemia and the hearts were removed to detect the NF-kB activity and expression of LC3-Ⅱ and cathepsin B. The left animals in each group were sacrificed at 2 h of reperfusion and the hearts were removed to determine the myocardial infarct size （by TTC staining）. Results Compared with group S, the myocardial infarct size was significantly increased at 2 h of reperfusion in the other groups, and the NF-kB activity was significantly increased and the expression of LC3-Ⅱ and cathepsin B was up-regulated immediately be- fore ischemia in group SEVO （P 〈 0.05）. Compared with group I/R, the NF-kB activity was significantly in- creased and the expression of LC3-Ⅱ and cathepsin B was up-regulated immediately before ischemia, and the myo- cardial infarct size was significantly reduced at 2 h of reperfusion in group SEVO （P 〈 0.05）. Compared with group SEVO, the NF-kB activity was significantly decreased and the expression of LC3-Ⅱ and cathepsin B was down-regulated immediately before ischemia, and the myocardial infarct size was significantly increased at 2 h of reperfusion in DMSO, PTN and PTN ＋ SEVO groups （ P 〈 0.05）. Conclusion NF-kB signaling pathway and au- tophagy are involved in inhaled sevoflurane-produced delayed myocardial protection in rats. Key words: Anesthetic, inhalation; Myocardial reperfusion injury; NF-kappa B