| Objective:To investigate the effect of exenatide preconditioning on myocardialischemia reperfusion injury in rats and related mechanismsMethods:Thirty—six healthy male SD rats were divided into sham-operated group,model group,and experimental group by table of random number?n=12 each?.The rats in sham-operated group were anesthetized for 150mins only with chest opened and without Ligation of the left anterior descending coronary artery.The rats in model group were established by occlusion of the left anterior descending coronary artery for 30mins and reperfusion for 120mins.The rats in experimental group were treated with exenatide(10ug·kg-1,sc,dissolved in sterile saline)1h before ischemia,thenfollowed by occlusion of the left anterior descending coronary artery for 30mins and reperfusion for120mins.The sham-operated group and the model group were given the same amount of normal saline as the balance control.HE?hematoxylin-eosin?staining method was used to observe cardiomyocyte status under optical microscope;Myocardial tissue samples were stained with TTC to measure the myocardial infarction area;protein expression of Cysteinyl aspartate-specific protease-3?caspase-3?and p53 was analyzed by immunohistochemical technique respectively;enzyme linked immunosorbent assay were used to detect serum superoxide dismutase?SOD?activity,the concentration of serum malondialdehyde?MDA?,and the activity of lactate dehydrogenase?LDH?,creatine kinase?CK?and Myeloperoxidase?MPO?.Results:1.Myocardial fiber structure of the rats in the sham-operated group clear and neat,there were no edema,interstitial inflammatory cell infiltration;myocardial fiber structure of the rats in model group disorder,fracture,and have highly cellular edema,interstitial infiltration of inflammatory cells;myocardial fiber structure of rats in the experimental group is normal,the cells are mild edema,and a fewinflammatory cells were infiltrated.the degree of myocardial damage of experimental group was significantly reduced?HE staining method2.Compared with the model group,the myocardial infarct area of the experimental group was significantly lower by TTC staining method?38±4%in the experimental group,52±4%in the model group,P<0.05?,The difference was statistically significant.3.Compared with the model group,protein expression of caspase-3 and p53 in experimental group was significantly downregulated?0.18±0.02?0.24±0.03 in the experimental group,respectively,0.26±0.03?0.37±0.02 in the model group,P<0.05?.The difference was statistically significant.4.Comparedwiththemodelgroup,SODactivitywassignificantly increased(111.00±4.85 u·mL-11 in the experimental group,62.20±4.82 u·mL-1in the modelgroup,P<0.05).MDA concentrationwassignificantlydecreased(2.58±0.29nmoL·mL-11 in the experimental group?3.96±0.47nmoL·m L-1in the model group,P<0.05).the activity of LDH,CK and MPO was significantly decreased in experimental group compared to model group(6383.57±248.15 U·L-1?1801.00±63.67U·L-11 and 31.97±4.14 U·L-11 in experimental group,respectively,8210.54±125.35 U·L-1?3015.66±178.73 U·L-11 and 62.57±7.71 U·L-1in the model group,P<0.05).The difference was statistically significant.Conclusion:Exenatide preconditioning protects myocardium against myocardial ischemia reperfusion injury?MIRI?possibly through reducing cardiomyoeytes apoptosis,resisting oxidation and showing anti-inflammatory action. |
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