The effect of sevoflurane on vascular endothelial injury in myocardial ischemia-reperfusion rats based on JAK2/STAT3 pathway

Wei Hong; Wang Junpeng; Zhou Yuyang

doi:10.3969/j.issn.1674-4055.2023.09.13

Abstract：Objective To investigate whether sevoflurane can reduce vascular endothelial injury in myocardial ischemia-reperfusion injury(MIRI)rats by regulating the protein tyrosine kinase 2(JAK2)/signal transduction and activator of Transcription 3(STAT3)signaling pathway.Methods Sixty rats were randomly divided into sham operation group,model group,sevoflurane group,inhibitor group and inhibitor + sevoflurane group,with 12 rats in each group.The MIRI model was established by ligation of the left anterior descending coronary artery in the remaining groups except the sham operation group.The rats in the model group and the sham operation group were injected with 1 ml of normal saline through the tail vein 2 h before the experiment,and inhaled pure oxygen for 3 min at the beginning of end-ischemia reperfusion.In sevoflurane group,1 ml of normal saline was injected into the tail vein 2 h before the experiment,and 2%sevoflurane was inhaled for 3 min at the beginning of end-ischemia reperfusion.Rats in the inhibitor group were injected with 3 mg/kg AG490 through the tail vein 2 h before the experiment;rats in the inhibitor+sevoflurane group were injected with 3 mg/kg AG490 through the tail vein 2 h before the experiment;rats in the inhibitor+sevoflurane group were injected with 2%sevoflurane for 3 min at the beginning of end-ischaemia reperfusion.The rats in the model group and the sham operation group were injected with 1 mL of normal saline through the tail vein 2 h before the experiment,and inhaled pure oxygen for 3 min at the beginning of end-ischemia reperfusion.Left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),left ventricular end-systolic diameter(LVESD)and left ventricular end-diastolic diameter(LVEDD)were detected by echocardiography,and myocardial infarction size was detected by TTC staining,Serum levels of endothelin-1(ET-1),thromboxane A2(TXA2)and prostacycline(PGI2)were detected by ELISA.Tunel staining was used to detect the apoptosis of myocardial cells in each group,and western blot was used to detect the relative expression of p-JAK2 and p-STAT3.Results Compared with the sham operation group,the contents of LVEF,LVFS,PGI2,and the relative expression of p-JAK2 and p-STAT3 protein in the model group were decreased,LVESD and LVEDD were increased,and the apoptosis rate of cardiomyocytes,TXA2 and ET-1 contents were increased(P<0.05).Compared with the model group,the contents of LVEF,LVFS,and PGI2 and the relative expression of p-JAK2 and p-STAT3 protein in the sevoflurane group were increased,LVESD and LVEDD were shortened,myocardial infarction area was decreased,myocardial cell apoptosis rate,TXA2,and ET-1 contents were decreased(P<0.05).Compared with the inhibitor group,the contents of LVEF,LVFS,and PGI2 and the relative expression of p-JAK2 and p-STAT3 protein in the inhibitor + sevoflurane group were increased,LVESD and LVEDD were shortened,myocardial infarction area was decreased,myocardial apoptosis rate,TXA2,and ET-1 contents were decreased(P<0.05).Compared with the sevoflurane group,the contents of LVEF,LVFS,and PGI2 and the relative expressions of p-JAK2 and p-STAT3 protein in the inhibitor + sevoflurane group were decreased,LVESD and LVEDD were increased,and the apoptosis rate of cardiomyocytes,TXA2 and ET-1 contents were increased(P<0.05).Conclusion Sevoflurane can ameliorate vascular endothelial injury,decrease cardiomyocyte apoptosis rate,and improve cardiac dysfunction in MI/RI rats,possibly by activating JAK2/STAT3 signaling pathway.