Experimental Study On The Mechanism Of Action Of Sitagliptin And Metformin On Myocardial Cells In Diabetic Cardiomyopathy Mice

ObjectivesTo investigate the protective effect of sitagliptin on diabetic cardiomyopathy(DCM)and whether the effect is achieved by regulating survival kinase activity or mediating apoptosis of cardiomyocytes.MethodsThe diabetic mouse models were induced by Intraperitoneal administration of streptozotocin(STZ).Diabetic mice were given either Sitagliptin or metformin.Serum biomarkers were tested to assess the level of myocardial damage,and HE staining was used to observe the degree of myocardial damage.Immunological methods were used to detect myocardial casapse-3,BAX,Bcl-2 and p-BAD.The expression and phosphorylation of p-AMPK、Akt、LKB-1、GSK-3βand p38 MAPK were detected.ResultsThe HW/BW ratio of the sitagliptin and metformin treatment group was lower than that of diabetic mice(P<0.05).The level of GLP-1 was increased after treatment with siglitine and metformin compared with mice in the diabetic group.Compared with the diabetic mice,sitagliptin and metformin reduced the level of CK-MB and c Tn-Ⅰ(P<0.05)and serum FFAs level(P<0.01)of diabetic mice was decreased by treatment with sieglitine and metformin(P<0.01).Immunochemical showed that the expression intensity of caspase-3and BAX decreased significantly after treatment with metformin and siglittin,while the level of Bcl-2 and p-BAD increased.Untreated diabetic mice showed significantly lower levels of p-Akt,p-AMPK,p-GSK-3β,LKB-1,and higher levels of p-p38αMAPK(P<0.001).The levels of p-Akt,p-AMPK,p-GSK-3β,LKB-1protein increased significantly after treatment with siglitine and metformin,whilethe levels of p-p38αMAPK decreased(P<0.001ConclusionsSitagliptin can reduce the the apoptosis of cardiomyocytes in DCM,the molecular mechanism may be related to restore phosphorylation(activated)AMPK and Akt,inactivated GSK-3βand p38?AMPK..