The Expression Of Corin In The Myocardial Of Rats With Diabetic Cardiomyopathy

ObjectiveDiabetes mellitus(DM)is a chronic metabolic disease characterized by hyperglycemia as a consequence of defects in insulin secretion,insulin resistance.Recently,the incidence of diabetes has gradually increased,while cardiac complications are the leading cause of mortality in diabetic patients.Diabetic cardiomyopathy(DCM)is a major complication in diabetic patients,which is characterized by myocardial left ventricular dysfunction.Several studies have demonstrated that activation of natriuretic peptide system play a very important role in heart failure.A newly identified enzyme Corin can converte pro-ANP to active ANP.Still,the role of Corin in DCM have not been reported.In this study,we established the type 1 DM model by a single tail vein injection of streptozocin(STZ),and investigated the expression of Corin and ANP in the myocardium in diabetic rats.To further elucidate the role of Corin in DCM.MethodsMale Sprague-Dawley rats equilibrated to surroundings for one week before experiments.Rats were randomly divided into two groups: control group(n=5)and DM group(n=15).Diabetes was induced by single tail vein injection of STZ(45 mg/Kg)dissolved in citrate buffer(0.1 mol/L,PH 4.2).Control groups were injected with an equal volume of citrate buffer alone.72 hours after STZ injection,rats with hyperglycemia(blood glucose≥16.7 mmol/L)were considered diabetic.After diabetes induction,fast blood glucose,body weight,urine glucose were detected every week.Left ventricular function were examined by using transthoracic echocardiography.Control and DM rats were sacrificed at 12 weeks of STZ-induced diabetes,and heart tissue samples were harvested.Heart tissue were fixed and dehydrated through a graded series of ethanols,embedded in paraffin,sectioned and mounted on glass slides.HE staining and Masson staining were performed to evaluate the pathological changes of heart tissue.Immunohistochemistry was used to detected the protein expression of Iso-lectin B4,Corin and ANP.Results1.Type 1 DCM model was successfully established.Glucose level was significantly elevated in DM group than control group after STZ injection(P<0.05).Urine glucose of DM group was positive.Body weight in DM group was significant decreased compared with control group(P<0.05).2.Echocardiography examination showed decreased E/A,fractional shorting(FS)and ejection fraction in DM group(P<0.05).LVIDs was increased in DM group.3.Compared with control group,the heart weight to body weight ratio were increased in DM groups(P<0.01).HE staining showed that myocytes from control group arranged regularly,and LV myocyte size was normal.The myocyte in DM group arranged irregularly and LV myocyte size was higher.Masson staining showed DM group became cardiac fibrosis after 12 weeks of STZ-induced diabetes.4.Immunofluorescent staining revealed Corin expression in heart tissue.5.The DM group showed reduced levels of Corin protein.6.The DM group showed reduced levels of ANP protein.7.Iso-lectin B4 staining showed reduced densities of capillaries in diabetic rats.Conclusions1.Type 1 DCM rat model was successfully established at 12 week after STZ injection.2.DCM rats showed impaired cardiac systolic function.3.The expression of Corin and ANP in heart tissue decreased in DM group.These results indicate that Corin and ANP may play an important role in the pathogenesis of DCM.