Protective Effect Of Berberine On The Heart Of Diabetic Cardiomyopathy Rats And Its Effect On Cardiac AMPK-ACC-CPT1 Signaling Pathway In Heart

Diabetes cardiomyopathy is a heart disease caused by diabetes alone,which can cause dysfunction of systolic and diastolic functions and even death from severe heart failure.There are many pathogenesis of DCM,and the role of lipid metabolism disorder in the formation of DCM has been recognized.Berberine is the main effective component in Chinese herbal medicine coptis.Modern studies have proved that berberine has the effect of reducing blood lipid in diabetic patients.In this study,whether berberine has a protective effect on diabetic cardiomyopathy rats in vivo and in vitro and the effect on AMPK-ACC-CPT1,a lipid metabolism pathway,was discussed,providing new ideas for the prevention and treatment of DCM in the future.1 ObjectiveTo study the effect of berberine on diabetic cardiomyopathy and the effect on AMPK-ACC-CPT1 metabolic pathway in heart.2 MethodsThe vivo experiment was to establish a diabetic rat model by streptozocin(STZ)combined with high-sugar and high-fat diet,and then continue to feed the high-sugar and high-fat diet for 12 weeks to induce the DCM model.During the induction model,the drug-administered group was given BBR intragastrically.After the test,the rat serum fasting blood glucose(FBG),triglyceride(TG),cholesterol(cholesterol,TC),free fatty acid(free fatty acid,FFA),creatine kinase isoenzyme(CK-MB),cardiac cadherin I(CTn I),lactic dehydrogenase(LDH),glutamic oxalacetic transaminase(glutamic oxalacetic transaminase,AST)were measured,echocardiogram was used to measure the contractile and diastolic function of the rat,and the heart weight/body weight ratio(HW/BW)was calculated.Myocardial tissue damage was observed by HE staining.Myocardial fibrosis was observed by Masson staining.The ultrastructure of the heart was observed by electron microscopy.The expressions of P-AMPK,AMPK,P-ACC,ACC,CPT1 were detected by Western blot.The vitro experiments were performed to screen the suitable high glucose concentration and time of induction of DCM model.The effective concentration of BBR on H9c2 cardiomyocytes was investigated.The expression of P-AMPK,AMPK,P-ACC,ACC and CPT1 induced by high glucose was detected by Western blot.And the effect of BBR administration on the expression of these proteins.3 ResultsIn vivo experiments found that BBR administration can significantly alleviate hyperglycemia caused by DCM,hyperlipidemia and reduce the content of myocardial enzymes in serum,increase the contraction and relaxation function of rat heart,reduce the proportion of heart in body weight,and reduce the fiber of myocardial And damage.Western blot analysis showed that berberine could increase the phosphorylation level of AMPK and ACC in the DCM group,increase the expression of CPT1.In vitro results showed that the induction of high glucose 50 m M for 24 h reduced the viability of H9c2 cardiomyocytes and the expression of P-AMPK.When BBR concentration of 25 μM,50 μM,and 100 μM were added,cell viability and P-AMPK levels were significantly improved.Western blot showed that the expression level of AMPK-ACC-CPT1 pathway was down-regulated during high glucose induction,and BBR could increase the phosphorylation of AMPK and ACC and promote the expression of CPT1.4 ConclusionBerberine has protective effect on DCM and can upregulate the activity of AMPK,ACC and CPT1.