Protection Of Acacetin Against Diabetic Cardiomyopathy

Introduction:Diabetic cardiomyopathy is a diabetic complication that causes cardiac structural and functional abnormalities independent of disorders such as coronary atherosclerosis and hypertension,and is the most important factor in the development of heart failure in diabetic patients.Energy metabolism disorders and increased oxidative stress are the main causes of their development.Previous studies have shown that the natural flavonoid acacetin exerts cardio-protective effects through antioxidants.This study aims to investigate whether acacetin can improve cardiomyopathy caused by hyperglycemia in rat diabetic cardiomyopathy,and to explore the potential molecular mechanisms in cultured cardiomyocytes.Methods:In cultured primary neonatal rat cardiomyocytes and H9C2 rat cardiomyoblasts,cellular injury was induced by high glucose(33 mmol/L)to determine whether acacetin protects against cell injury by high glucose culture.Diabetic cardiomyopathy was established by intraperitoneal injection of streptozotocin(STZ)to observe whether acacetin might improve diabetic cardiomyopathy.Multiple technologies including biochemical and molecular biological techniques,small animal echocardiography,enzymatic examination,etc.were utilized to investigate the effects of acacetin on heart function and myocardial damage induced by hyperglycemia,and to explore energy metabolism and oxidative stress-related signaling molecules.Results:In cardiomyocytes,acacetin antagonized the cardiomyocytes viability reduction,reversed the decreased antioxidant-related proteins(SOD1,SOD2),anti-apoptosis-related proteins(Bcl-2),and energy metabolism-related proteins(PPAR-a,PPAR-y),and the increase of the apoptosis-associated protein(BAX)induced by high glucose.In STZ-induced diabetic rats,the cardiac contractile function index,cardiac ejection fraction(EF),was significantly reduced(62.3%±4.1%vs.80.3%± 1.8%of control),while acacetin significantly improved cardiac function in rats(to 78.0%±2.4%).Blood glucose was significantly elevated in the DM group;however,acacetin had no effect on blood glucose,but significantly decreased triglyceride(TG)and total cholesterol(TC).Acacetin treatment decreased the increase of serum angiotensin Ⅱ(Ang Ⅱ),inflammatory factor(IL-6)and oxidative stress(MDA)levels caused by hyperglycemia,and reversed the reduced total SOD activity.In diabetic hearts,IL-6 and BAX protein increased,SOD2,PPAR-a and pAMPK decreased,which were reversed in animals treated with acacetinConclusions:Acacetin protects against cardiomyocyte injury by high glucose and cardiomyopathy in diabetic rats,which may be related to the increase of phosphorylation of AMPK protein,SOD1 and SOD2,thereby decreasing oxidative stress,inflammatory factors,and apoptosis.