Leptin Pretreatment Induces Cardiomyocyte Autophagy To Reduce Myocardial Ischemia Reperfusion Injury

Objective: Acute myocardial infarction is a common pathological phenomenon in clinical practice.Although effective treatment and reasonable operation can improve the symptoms of patients with myocardial ischemia,However,Myocardial ischemia reperfusion injury(MIRI)caused by reperfusion significantly affected the outcome of patients.Autophagy,as an adaptive response to the cell environment,plays an important role in the process of MIRI.By studying the effect of leptin on autophagy of cardiomyocytes in MIRI,this study provides more theoretical basis and more sufficient experimental basis for the clinical application of leptin in MIRI.Methods: Earlier,through searching GEO database,we found that The Recombinant autophagy related protein 16 like protein(ATG16L1)allelic homozygote of recombinant autophagy related protein 16 like protein(ATG16L1)was similar to the recombinant autophagy deficient Pani cells,which showed significantly increased leptin protein expression level.That is,there is a certain correlation between the strength of autophagy and the expression of leptin gene.Therefore,this study observed the effect of leptin on autophagy of myocytes through in vivo experiments,and then explored the effect of leptin on MIRI myocytes.Thirty-six adult male SD rats were randomly divided into A,B and C groups with 12 rats in each group.Group A was sham operation group,only thoracotomy without vasculature;Group B was the I/R group.The I/R model was established by the rope method after thoracotomy.Group C was LEP+I/R group.LEP pretreatment was performed before I/R model was established.TTC staining was used to detect myocardial cell activity,HE staining was used to detect myocardial injury degree,ELISA was used to detect the levels of serum myocardial injury markers CK-MB and c Tn I,and Western blotting was used to detect the protein expressions of p62,LC3-B and ATG16L1 in rat myocardial cells.The p62,LC3-B and ATG16L1 genes in rat cardiomyocytes were detected by real-time quantitative PCR.Results: TTC staining results showed that compared with group A,the myocardial infarction area and myocardial injury score of rats in groups B and C were increased(P < 0.05).Compared with group B,the myocardial infarction area of rats in group C was reduced and the myocardial injury score was significantly reduced [(17.83 ± 1.86)% vs(32.33 ± 2.29)%].HE staining showed that myocardial fibers in group A were arranged neatly,without obvious inflammatory reaction and erythrocyte exudation.In group B,the myocardial fibers were disordered,some myocardial cells were ischemic and necrotic,and obvious bleeding and necrotic foci could be observed.The degree of myocardial cell edema in group C was mild,the degree of myocardial fiber floc was not obvious,and the degree of injury was significantly improved compared with group B [(0.67 ±0.41)% vs(1.67 ± 0.75)%].ELISA results showed that compared with group A,the level of serum myocardial injury marker CK-MB in groups B and C was significantly increased.Compared with group B,the level of CK-MB in serum myocardial injury marker of rats in group C was significantly decreased,and the level of c Tn I in serum myocardial injury marker of rats in three groups was not significantly different.Western blotting and real-time quantitative PCR detection results showed that:Compared with group A,the expression of p62 in protein and m RNA levels in groups B and C was significantly decreased,and the expression of ATG16L1 and LC3-B in protein and m RNA levels was significantly increased.Compared with group B,the expression of P62 in group C was significantly decreased,LC3 B was significantly increased,and the expression of ATG16L1 was slightly increased.Conclusions: 1.Leptin protein expression was positively correlated with the number of autophagosomes formed,that is,the higher the leptin protein expression level,the greater the autophagy intensity of myocardial cells.2.Leptin pretreatment can inhibit inflammatory cell infiltration and erythrocyte exudation,and reduce the degree of myocardial cell edema.3.Leptin pretreatment can reduce the expression level of serum myocardial injury markers and reduce the degree of myocardial cell injury in rats.4.Leptin preconditioning may reduce myocardial ischemia reperfusion injury by inducing autophagy of cardiomyocytes,thus protecting cardiomyocytes.