| Objective:Myocardial ischemia-reperfusion injury is a high incidence of myocardial injury in coronary heart disease and its treatment.Sevoflurane postconditioning is a drug intervention strategy which can effectively reduce myocardial ischemia-reperfusion injury.GLP-1R signal pathway plays an important role in myocardial protection.In this study,a rat model of myocardial ischemia-reperfusion injury was established to explore the role of GLP-1R signal pathway in reducing myocardial ischemia-reperfusion injury by sevoflurane postconditioning.Methods:Eighty SPF adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 300-340 g,were divided into 4 groups(n=20 each)by a random number table method: sham operation group(group S),myocardial ischemia-reperfusion group(group I/R),myocardial ischemia-reperfusion+ sevoflurane postconditioning group(group ISP),myocardial ischemia-reperfusion+ sevoflurane postconditioning+ GLP-1R antagonist group(group ISPE).The myocardial ischemia-reperfusion injury model in rats was established by ligating the left anterior descending branch of the coronary artery for 40 min followed by 2 h reperfusion.In group ISP,the rats inhaled 2.4% sevoflurane for 15 min at the beginning of reperfusion.In group ISPE,50 μg/kg Exendin9-39(dissolved in 1ml 0.9% normal saline)was injected intraperitoneally once a day from 28 days before the establishment of the model and at the beginning of ischemia,and the other treatments were the same as the group ISP.Abdominal aorta blood samples were collected immediately after reperfusion to detect the serum levels of creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH).Then the rats were sacrificed and the heart tissue was obtained.The ultrastructure of cardiomyocytes was observed under transmission electron microscope,the infarct size was measured by TTC staining,the expression of GLP-1R,cyclic adenosine monophosphate(c AMP),protein kinase A(PKA),c AMP response element-binding protein(CREB),phospho-CREB(p-CREB),B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)in myocardium was detected by Western blot,and the ratios of p-CREB/CREB and Bcl-2/Bax were calculated.Results:1.Compared with group S,the levels of CK-MB and LDH,the percentage of myocardial infarct size,and the expression of GLP-1R were significantly increased,and the expression of c AMP and PKA,the ratio of p-CREB/CREB and the ratio of Bcl-2/Bax were decreased in group I/R(P<0.05).2.Compared with group I/R,the levels of CK-MB and LDH,and the percentage of myocardial infarct size were significantly decreased,the expression of GLP-1R,the ratio of p-CREB/CREB and the ratio of Bcl-2/Bax were increased in group ISP(P<0.05).3.Compared with group ISP,the levels of CK-MB and LDH,and the percentage of myocardial infarct size was significantly increased the expression of GLP-1R,the ratio of p-CREB/CREB and the ratio of Bcl-2/Bax were decreased in group ISPE(P<0.05).Conclusion:Sevoflurane postconditioning can inhibit cardiomyocyte apoptosis and alleviate myocardial ischemia-reperfusion injury in rats by activating GLP-1R signal pathway. |
