Study On The Effect And Mechanism Of DPP-4 Inhibitor On Myocardial Ischemia-Reperfusion Injury

Objective By ligating the artery of the left anterior descending branch of the rat heart,the p athological process of cardiac ischemia injury was simulated,and the effect of dipe ptide peptidase-4 inhibitor on myocardial ischemia reperfusion injury in rats was pr eliminarily studied,so as to provide experimental basis for the study of a new met hod to reduce myocardial ischemia reperfusion injury.Methods Thirty SD rats were randomly divided into 5 groups: sham operation group,ischemia-reperfusion model group,sitagliptin 5mg·kg-1 preconditioning group,sitagliptin10mg·kg-1 preconditioning group and sitagliptin 15mg· kg-1 preconditioning group.Rats in the sitagliptin group were given 5mg·kg-1,10mg·kg-1,and 15mg·kg-1 by gavage at 1week before surgery,and the other two groups were given 0.9% sodium chloride by gavage.The pathological process of human cardiac ischemia injury was successfully simulated by ligating the artery of the left anterior descending branch of the rat heart and reperfusion for 2h after ischemia for 30 min.ST segment changes were monitored by ecg,and oxidative stress indexes such as myocardial enzyme and superoxide dismutase were detected.The myocardial infarction area was measured by Evans blue-ttc method,and morphological changes of myocardial ischemia-reperfusion were observed by HE staining.Results Compared with sham operation group,ischemia reperfusion model group,sitagliptin5mg·kg-1 preconditioning group,sitagliptin 10mg·kg-1 preconditioning group and si tagliptin 15mg·kg-1 preconditioning group aspertate aminotransferase,creatine kinase,creatine kinase isoenzyme,lactate dehydrogenase and a-hydroxybutyrate dehydrogena se increased(P<0.05),the activities of the three enzymes catalase,superoxide dism utase and glutathione peroxidase all decreased(P<0.05),but the content of malondi aldehyde increased(P<0.05).Compared with the ischemia-reperfusion model group,the levels of serum aspartate aminotransferase,creatine kinase,creatine kinase isoen zyme,lactate dehydrogenase,and a-hydroxybutyrate dehydrogenase in rats in each s itagliptin administration group all decreased(P<0.05),and increased the activities of the three antioxidant enzymes catalase,superoxide dismutase and glutathione peroxi dase to different degrees,and reduced the content of malondialdehyde(P<0.05),and dose-dependent.After Evans blue-ttc staining,most of the myocardial tissues in the ischemia-reperfusion model group were stained with gray-white.In the sitagliptin pr etreatment group,as the drug concentration increased,the gray-white portion of the low,medium,and high drug administration groups gradually decreased.Compared with the ischemia-reperfusion model group,the sitagliptin pretreatment group reduce d the infarct size of ischemia-reperfusion injury in rats(P<0.05);Compared with the sitagliptin 10mg·kg-1 pretreatment group,the infarct area of rats in the sitagliptin 5mg·kg-1 pretreatment group increased,while the infarct area of rats in the sitaglipti n 15mg·kg-1 pretreatment group decreased(P<0.05).After HE staining,the morpho logy of the myocardium in the sham operation group was normal,but the myocard ial fibrosis in the ischemia-reperfusion model group was obvious,and the cells wer e severely degenerated.However,after pretreatment with sitagliptin,with the increa se of the dosage,the myocardial pathological changes of each administration group gradually reduced.Conclusion Sitagliptin,as a representative drug for clinical use of dipeptidyl peptidase-4 inhibitors,can reduce the production of myocardial enzymes caused by ischemia-reperfusion injury,reduce the infarct size,reduce the index of oxidative stress,and gradually reduce the myocardial tissue lesions,and it is dose-dependent.Its mechanism of action on the heart may be related to the promotion of antioxidant enzyme activity and the reduction of lipid peroxidation.