| Objective:Discussing the relationgship between the protective effect of Sevoflurane on myocardium and hif2 α-AREG pathway.MethodsForty five healthy male SD rats,aged about 10-12 weeks,were randomly divided into five groups.After different treatments,left anterior descending coronary artery(LAD)was ligated to establish myocardial ischemia-reperfusion injury model.Lad was ligated for 40 minutes,and 2.4%(1mac)Sevoflurane was given at the beginning of reperfusion for 15 minutes.Sevoflurane was closed and reperfusion was continued for 105 minutes.Group A:sham operation group;Group B: ischemia-reperfusion injury group;Group C: ischemia reperfusion injury + Sevoflurane postconditioning group;Group D: ischemia reperfusion injury + Sevoflurane postconditioning + HIF2α Blocker group;Group E: ischemia reperfusion + Sevoflurane postconditioning + HIF2α Blocker + areg proteome.Compare the changes of mean arterial pressure(MAP)at 15 min after ischemia and before ischemia,compare the changes of MAP at 2 h afte Forty five healthy male SD rats,aged about 10-12 weeks,were randomly divided into five groups.After different treatments,left anterior descending coronary artery(LAD)was ligated to establish myocardial ischemiareperfusion injury model.Lad was ligated for 40 minutes,and 2.4%(1mac)sevoflurane was given at the beginning of reperfusion for 15 minutes.Sevoflurane was closed and reperfusion was continued for 105 minutes.Group: Sham group: lad was separated,only thread was put under lad,no ligation;I / R group: ischemia reperfusion injury group;Sevo group: ischemia reperfusion injury + sevoflurane postconditioning group;HIF2 α Group:ischemia reperfusion injury + sevoflurane postconditioning + HIF2 α Blocker group;AREG group: ischemia-reperfusion injury + sevoflurane postconditioning + hif2 α Blocker + areg proteome.To explore the protective effect of sevoflurane on myocardium and whether the protective effect of sevoflurane is related to hif2,the changes of mean arterial pressure(map),the ratio of infarcted myocardium to left ventricle and the protein expression of Bax,Bcl-2 and areg in each group were compared α-Areg pathway.r reperfusion,and compare the changes of the ratio of infarcted myocardium to left ventricle were compared,compare the changes of the protein expressions of Bax,Bcl-2 and AREG among the groups,to explore whether Sevoflurane can protect myocardium from HIF2α-AREG pathway.Results1.Hemodynamic changes of rats in each group: time,grouping,interaction of time and grouping had no significant effect on heart rate(P > 0.05),but had significant effect on mean arterial pressure(F time = 101.41,F groups = 10.23,F interaction = 6.93,P < 0.05).There was no significant difference in heart rate and mean arterial pressure before ischemia in each group(P > 0.05).Except for sham group,the mean arterial pressure of rats in other groups at different time periods was significantly different(F = 16.07-34.08,P < 0.05).The mean arterial pressure of rats in each group at 15 min of ischemia and at the end of 2 h of reperfusion decreased to varying degrees compared with that before ischemia(P < 0.05).The mean arterial pressure of rats in sevo group and areg group at the end of 2 h of reperfusion increased significantly compared with that of rats in group 15 min of ischemia(P < 0.05).At the end of 2 h of reperfusion,compared with I / R group,the mean arterial pressure in sevo group and areg group increased significantly(F = 13.62,P < 0.05),while that in hif2 group decreased significantly(P < 0.05)α There was no significant difference between the two groups(P > 0.05).2.The ratio of infarcted myocardium to left ventricle in each group: there was no significant difference in total left ventricular weight among the groups,but there was significant difference in myocardial infarction area among the groups(F = 193.26,P <0.05).Compared with group C and group E,the ratio of myocardial infarction to left ventricle in group B was significantly increased(t = 20.01,P < 0.05).These results indicate that Sevoflurane and areg can reduce myocardial ischemia-reperfusion injury and infarct size.The ratio of infarcted myocardium to left ventricle in group C was significantly lower than that in group D(t = 14.24,P < 0.05),indicating that HIF2α blockers participate in and counteract the cardioprotective effect of Sevoflurane;The ratio of myocardial infarction to left ventricle in group D was lower than that in Group E(t = 15.17,P < 0.05),which also proved the myocardial protective effect of AREG.3.The protein expression levels of Bax and Bcl-2 in myocardial tissue of rats in each group: compared with group B,the ratio of Bax / Bcl-2 in group C was significantly lower(t = 5.04,P < 0.05).It is proved that Sevoflurane has the effect of anti apoptosis and myocardial protection.Compared with group C,the ratio of Bax / Bcl-2 was up-regulated in group D and down regulated in Group E(t = 6.79,5.47,P < 0.05).These results indicate that HIF2α blocker can positively regulate cell apoptosis,while areg can inhibit cell apoptosis.4.The expression level of AREG protein in myocardial tissue of rats in each group: the relative expression of areg protein in group D was lower than that in group C(t = 9.27,P <0.05).The relative expression of areg protein in Group E was higher than that in group D(t = 5.65,P < 0.05).It is directly proved that HIF2α is the upstream pathway of areg.5.The morphology of myocardial cells in each group was compared under light microscope:compared with group B,the structure of cardiomyocytes in group C was more complete under light microscope.Compared with group C,group D had disordered cardiomyocytes,increased pyknosis and neutrophil aggregation.Compared with group D,cardiomyocytes in Group E were more orderly and neutrophils were less aggregated.ConclusionSevoflurane postconditioning can reduce myocardial ischemia-reperfusion injury;HIF2α inhibitor can counteract the myocardial protective effect of Sevoflurane and aggravate the myocardial injury.The recombinant AREG protein can improve cardiac function and enhance hemodynamic protection on the basis of HIF2α inhibitor counteracting Sevoflurane myocardial protection,and HIF2α-AREG pathway is involved in the myocardial protection of Sevoflurane. |
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