a Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, China, 266000.
b Department of Operating Room, Affiliated Hospital of Qingdao University, Qingdao, China, 266000.
Can J Physiol Pharmacol. 2019 May;97(5):345-351. doi: 10.1139/cjpp-2018-0016. Epub 2018 Jun 12.
We aimed to investigate whether the cardioprotection of sevoflurane against ischemia-reperfusion (IR) injury is via inhibiting endoplasmic reticulum stress. The rat in vivo model of myocardial IR injury was induced by ligation of the left anterior descending coronary artery. Sevoflurane significantly ameliorated the reduced cardiac function, increased infarct size, and elevated troponin I level and lactate dehydrogenase activity in plasma induced by IR injury. Sevoflurane suppressed the IR-induced myocardial apoptosis. The increased protein levels of glucose-regulated protein 78 and C/EBP homologous protein (CHOP) after myocardial IR were significantly reduced by sevoflurane. The protein levels of phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2 (eIF2α), and activating transcription factor 4 (ATF4) were significantly increased in rats with IR and attenuated by sevoflurane treatment. The phosphorylation of Akt was further activated by sevoflurane. The cardioprotection of sevoflurane could be blocked by wortmannin, a PI3K/Akt inhibitor. Our results suggest that the cardioprotection of sevoflurane against IR injury might be mediated by suppressing PERK/eIF2a/ATF4/CHOP signaling via activating the Akt pathway, which helps in understanding the novel mechanism of the cardioprotection of sevoflurane.
我们旨在研究七氟醚对缺血再灌注（IR）损伤的心脏保护作用是否通过抑制内质网应激实现。通过结扎左前降支冠状动脉诱导大鼠体内心肌 IR 损伤模型。七氟醚显著改善了由 IR 损伤引起的心脏功能降低、梗死面积增大以及血浆中心肌肌钙蛋白 I 水平和乳酸脱氢酶活性升高。七氟醚抑制了 IR 诱导的心肌细胞凋亡。七氟醚显著降低了 IR 后心肌中葡萄糖调节蛋白 78 和 C/EBP 同源蛋白（CHOP）的蛋白水平增加。IR 大鼠中磷酸化蛋白激酶 RNA 样内质网激酶（PERK）、磷酸化真核起始因子 2（eIF2α）和激活转录因子 4（ATF4）的蛋白水平显著增加，并用七氟醚处理后减弱。七氟醚进一步激活了 Akt 的磷酸化。PI3K/Akt 抑制剂wortmannin 可阻断七氟醚的心脏保护作用。我们的研究结果表明，七氟醚对 IR 损伤的心脏保护作用可能是通过抑制 PERK/eIF2a/ATF4/CHOP 信号通路来实现的，该通路通过激活 Akt 通路，有助于理解七氟醚心脏保护作用的新机制。
