Study On The Mechanism Of Berberine Improving Cardiac Function In Diabetic Cardiomyopathy Rats By Regulating AMPK-AS160-GLUT4 Signaling Pathway

Diabetic cardiomyopathy(DCM)is one of the most serious complications of diabetes.It is a special heart disease caused by diabetes that accompanies or separates from vascular disease.It causes extensive myocardial foci based on metabolic disorders and microvascular disease.Sexual necrosis,subclinical cardiac function abnormalities,and eventually progress to heart failure,arrhythmia,and cardiogenic shock.The cause of diabetic cardiomyopathy is inconclusive.Studies have shown that chronic hyperglycemia can cause cardiomyocytes,fibroblasts,and endothelial cells to cause energy metabolism disorders.Too much fatty acid can enter the cardiomyocytes and cause lipotoxicity.Is an important cause of DCM.Berberine,the main component of Rhizoma Coptidis rhizome,is widely used to lower blood sugar and blood lipids.It can be traced back to the "Shen Nong Ben Cao Jing ".This study explores the therapeutic effects of berberine on diabetic cardiomyopathy and its effect on the glucose metabolism pathway AMPK-AS160-GLUT4 in vivo and in vitro,providing new ideas for the prevention and treatment of DCM.ObjectiveIn this study,we combined in vivo and in vitro experiments to investigate the effect of berberine on the improvement of cardiac function in diabetic cardiomyopathy rats and on the AMPK-AS160-GLUT4 signaling pathway.The purpose is to verify the feasibility of traditional Chinese medicine in the treatment of DCM,and to provide new ideas and theoretical basis for the prevention and treatment of DCM.MethodsA streptozotocin(STZ)supplemented with high-sugar and high-fat diet was used to establish a diabetes rat model of SD,and then fed to the high-sugar and high-fat diet to induce rats to induce DCM for 12 weeks.BBR was administered by intragastric administration.After 12 weeks of treatment,echocardiography was used to detect the contractile function of rats.Abdominal aortic blood was taken to measure fasting blood glucose(FBG),triglycerides(TG),free fatty acids(FFA),cholesterol(TC),and creatine kinase isoforms.Contents of enzymes(CK-MB),cardiac troponin I(c Tn?),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH);cardiac tissue was calculated to calculate the heart-to-body weight ratio,and the degree of myocardial damage was observed by HE staining and Van Gieson staining The degree of myocardial fibrosis,oil red O staining was used to observe fat deposition,and electron microscopy was used to observe cardiac ultrastructural damage.Western blot was used to detect P-AMPK,AMPK,P-AS160,AS160,GLUT4,and pyruvate dehydrogenase(PDH)expression.CCK-8 test screened the concentration and time of high glucose-induced H9c2,conducted in vitro experiments,screened the appropriate concentration of BBR effect in the same way,observed the GLUT4 content of H9c2 cells by laser confocal,detected the sugar uptake of H9c2 by 2-NBDG,and detected high glucose by Western blot The levels of PAMPK,AMPK,P-AS160,AS160,GLUT4,and PDH proteins were induced in H9c2 cells after BBR administration.ResultsIn vivo experiment1.The results of echocardiography showed that BBR can effectively enhance the cardiac contractility and improve the cardiac function of rats.2.Serum test results show that BBR can effectively reduce blood glucose and lipids in rats;reduce serum myocardial enzymes and improve cardiac contractility.3.Pathological section results show that BBR can improve cardiac injury,reduce myocardial fibrosis,and reduce fat deposition in rats.4.Western blot results showed that BBR can increase the phosphorylation of AMPK and AS160 in rat heart,promote the transport of GLUT4 membrane and increase the expression of PDH.In vitro experiments1.Induction of H9c2 cells with 50 m M glucose for 24 hours can reduce the viability of H9c2 cells.BBR at a concentration of 25 ?M,50 ?M,and 100 ?M can improve cell viability.2.Laser confocal analysis showed that BBR can increase the content of GLUT4 on H9c2 cell membrane.3.2-NBDG results showed that BBR can increase glucose uptake in H9c2 cells.4.The results of Western blot showed that high glucose induced inhibition of AMPK,AS160 phosphorylation,PDH,GLUT4 expression decreased,BBR intervention increased AMPK,AS160 phosphorylation,and up-regulated PDH,and promoted GLUT4 membrane transport.Conclusion1.BBR can effectively improve the heart function of rats,reduce fat deposition and fibrosis,protect heart tissue,and lower blood sugar.2.The ability of GLUT4 to transport membranes in the heart tissue of rats with diabetic cardiomyopathy is blocked.BBR can regulate downstream factors by activating AMPK,thereby promoting GLUT4 transport and improving energy metabolism disorders caused by glucose uptake disorders.3.In the state of DCM,the heart's PDH expression is inhibited,and glucose metabolism cycle disorders.BBR can effectively increase PDH activity,enhance mitochondrial ATP production,and protect the heart.