Effect of isoflurane on arresting ferroptosis and improving myocardial ischemia-reperfusion injury
OBJECTIVE To explore the protective effect of isoflurane on myocardial ischemia reperfusion(MI/R)injury and elucidate its potential mechanism from the perspective of ferroptosis.METHODS Healthy male Sprague-Dawley(SD)rats were used as research subjects at animal level and H9C2 cardiomyocytes as research subjects at cellular level.They were assigned into five groups of control,model,isoflurane,model+isoflurane and model+Ferrostatin-1.Myocardial infarct area was deter-mined after nitrotetrazolium blue chloride(NBT)stain.Morphological changes in myocardial tissue were observed after hematoxylin-eosin stain.Myocardial cell viability was determined by CCK-8 method.The levels of lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB)were measured by enzyme-linked immunosorbent assay(ELISA).The values of reactive oxygen species(ROS),malondialdehyde(MDA),Fe2+,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in myocardial tissue or H9C2 cells were detected by kits.Western blot was utilized for detecting the protein expres-sions of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and nuclear factor erythroid 2-related factor 2(Nrf2)in myocardial tissue or cells.RESULTS As compared with control group,model group had a spike in myocar-dial infarction area(P＜0.01),lowered myocardial cell activity(P＜0.01),sharp spike of LDH/CK-MB content(P＜0.01),spikes in ROS,MDA and Fe2+in myocardial tissue or cells(P＜0.01),lowered GSH-Px activity(P＜0.01)and down-regulations of SLC7A11,GPX4 and nuclear Nrf2 proteins(P＜0.01).As compared with model group,isoflurane and positive control groups showed declines in myocardial infarction(P＜0.01),greater myocardial cell viability(P＜0.01),declines in ROS,MDA and Fe2+in myocardial tissue or cells(P＜0.01),greater GSH-Px activity(P＜0.01)and spikes in SLC7A11,GPX4 and nuclear Nrf2 protein expression(P＜0.01).CONCLUSION Pretreatment with isoflurane may activate the Nrf2 pathway,enhance the expressions of SLC7A11 and GPX4 proteins,suppress ferroptosis in myocardial cells and thus exert protec-tive effects on MI/R injury.
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