Effect of sevoflurane on autophagy level in mice with myocardial ischemia-reperfusion injury
REN Nihui1, GUO Zhijia2, WANG Xin2, WANG Chenggang3, ZHANG Wenjie1, TIAN Shouyuan1
1. Department of Anesthesiology, Shanxi Medical University, Taiyuan 030001,China; 2. Department of Anesthesiology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China; 3. Department of Anesthesia and Surgery, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan 030012,China
Abstract：Objective From the perspective of PI3K/Akt/mTOR pathway, to explore the potential effect of sevoflurane on autophagy levels in mice with myocardial ischemia-reperfusion injury. Methods Twenty-four mice were randomly divided into 4 groups (n=6): sham operation group(only chest opening without ligation), ischemia-reperfusion group (ligating the left anterior descending coronary artery as ischemia-reperfusion operation under pentobarbital anesthesia), sevoflurane group (surgery under sevoflurane anesthesia), and sevoflurane+LY294002 group (LY294002, PI3K blocker, was injected daily one week before ischemia-reperfusion surgery and the rest was the same as in Sevoflurane group). Plasma was collected to detect the levels of myocardial injury markers, creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI). Myocardial tissue was detected by western blot method to detect autophagy markers, LC3 and Beclin1, and signaling pathway proteins, phosphatase 3-kinase (PI3K), protein kinase B (Akt), rapamycin (mTOR) total protein and phosphorylated protein levels. Results Compared with sham operation group, the levels of plasma CK-MB, cTnI, markers of cardiac autophagy LC3 and Beclin1 in the other three groups were significantly increased (P<0.05), and the ratios of phosphorylated PI3K, Akt and mTOR to total protein significantly decreased (P<0.05). Compared with sham operation group, the total protein levels of PI3K, Akt and mTOR in sevoflurane group were not significantly different. The levels of PI3K and Akt significantly increased (P<0.05), and the level of mTOR protein significantly decreased (P<0.05) in ischemia-reperfusion group. The level of PI3K in sevoflurane +LY294002 group significantly increased (P<0.05), and the protein levels of Akt and mTOR significantly decreased (P<0.05). Compared with ischemia-reperfusion group, plasma LEVELS of CK-MB and cTnI, LC3 and Beclin1 in sevoflurane group and sevoflurane +LY294002 group significantly decreased (P<0.05). Compared with the ischemia-reperfusion group, the ratio of phosphorylated PI3K, Akt and mTOR protein to total protein levels in sevoflurane group significantly increased (P<0.05). Compared with sevoflurane group, plasma LEVELS of CK-MB, cTnI, LC3 and Beclin1 in sevoflurane +LY294002 group significantly increased (P<0.05). The levels of phosphorylated PI3K, Akt and mTOR protein to total protein in sevoflurane +LY294002 group significantly decreased (P<0.05). Conclusions Sevoflurane inhibits the excessive autophagy induced by ischemia-reperfusion, and the possible mechanism is that it upregulates the phosphorylation level of PI3K/Akt/mTOR pathway protein.
Wu M Y, Yiang G T, Liao W T, et al. Current mechanistic concepts in ischemia and reperfusion injury[J]. Cell Physiol Biochem, 2018, 46(4): 1650-1667.
[2]
Shi H H, Wang Z Q, Zhang S. MiR-208a participates with sevoflurane post-conditioning in protecting neonatal rat cardiomyocytes with simulated ischemia-reperfusion injury via PI3K/AKT signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2020, 24(2): 943-955.
[3]
Qin J, Ma Q, Ma D. Low-dose sevoflurane attenuates cardiopulmonary bypass (CPB)- induced postoperative cognitive dysfunction (POCD) by regulating hippocampus apoptosis via PI3K/AKT pathway[J]. Curr Neurovasc Res, 2020, 17(3): 232-240.
[4]
Guo Z J, Guo Z. Non-excitatory electrical stimulation attenuates myocardial infarction via homeostasis of calcitonin gene-related peptide in myocardium [J]. Peptides, 2015, 65:46-52.
Aghaei M, Motallebnezhad M, Ghorghanlu S, et al. Targeting autophagy in cardiac ischemia/reperfusion injury: a novel therapeutic strategy[J]. J Cell Physiol, 2019, 234(10):16768-16778.
[7]
Du J, Li Y, Zhao W. Autophagy and myocardial ischemia[J]. Adv Exp Med Biol, 2020, 1207:217-222.
[8]
Lin X L, Xiao W J, Xiao L L, et al. Molecular mechanisms of autophagy in cardiac ischemia/reperfusion injury [J]. Mol Med Rep, 2018, 18(1): 675-683.
[9]
Wu S, Chang G, Gao L, et al. Trimetazidine protects against myocardial ischemia/reperfusion injury by inhibiting excessive autophagy [J]. J Mol Med (Berl), 2018, 96(8): 791-806.
Lu Y, Bu M, Yun H. Sevoflurane prevents hypoxia/reoxygenation-induced cardiomyocyte apoptosis by inhibiting PI3KC3-mediated autophagy[J]. Hum Cell, 2019,32(2):150-159.
[13]
Shi B, Ma M, Zheng Y, et al. mTOR and Beclin1: two key autophagy-related molecules and their roles in myocardial ischemia/reperfusion injury[J].J Cell Physiol, 2019,234(8):12562-12568.
[14]
Xu Z, Han X, Ou D, et al. Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy[J]. Appl Microbiol Biotechnol, 2020,104(2):575-587.
[15]
Zhang J, Zhang J X, Zhang Q L. PI3K/AKT/mTOR-mediated autophagy in the development of autism spectrum disorder [J]. Brain Res Bull, 2016, 125: 152-158.
2022, Vol. 33 
