The Study Of Protective Effect Of Huangqi San On Cardiomyopathy And Skeletal Muscle With Diabetes Mellitus Based On MG53 Protein

ObjectiveBased on the research and previous experiments,to study the protective effect of Huangqi San on cardiomyopathy and skeletal muscle with diabetes mellitus basede on MG53 protein.MethodsRats received high fat diet and Streptozocin(STZ)to reproduce the modelof type 2 diabetes mellitus rats,and were orally administered with drugs for sixteen consecutive weeks.Fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),free fatty acids(FFA),diacylglycerol(DAG),ceramide,homocysteine(Hcy)and histological features of myocardium and skeletal muscle were observed,Mitsugumin 53(MG53)and peroxisome prolifer-ationactivated receptor-α(PPAR-α)mRNA expression were observed by Real-time PCR,MG53,insulin receptor(IR),insulin receptorsubstrate-1(IRS-1),GLUT4、PPAR-α、CBS、CTH、MTHFR protein expression were observed by Western Blot,and try to investigate possible mechanism.Results1.Huangqi San(HQS)can significantly reduce weight of the model group,the results revealed HQS has a good weight loss effectiveness;the levels of FBG,TC,TG and LDL-C in HQS group were significantly reduced.OGTT results showed that HQS can better control of glucose tolerance in T2DM rats.2、The effects of glucose metabolism in diabetic myocardium and skeletal muscle tissue:there was proper decrease in PKC of myocardium and skeletal muscle tissue and HQS has different degrees improvement of MG53,IR,IRS-1,GLUT4 protein expression.3、The effects of fat metabolism in diabetic myocardium and skeletal muscle tissue:HQS has different degrees reduction of FFA、DAG、ceramide contents,there was remarkable down-regulation of MG53、PPAR-α mRNA,but there was no significant change of PPAR-α protein expression.4、The effects of protein metabolism in diabetic myocardium tissue:HQS can significantly reduce the level of Hcy,but the CBS、CTH、MTHFR protein expression has no significant change.5、The results of pathological morphology of metabolism and skeletal muscle tissue:HQS can improve diabetic model rats of metabolism and skeletal muscle in pathology.Moreover,HQS can significantly reduced myocardial collagen fibers and reducing the number of myocardial cell apoptosis.6、Comparaed with HQS(16w),HQS(23w)carried on drug intervention late 7w,at this time it is more serious,the study results show that levels of TC、TG、LDL-C、PKC、Hcy、FFA、ceramide and MG53mRNA,PPAR-α protein expression is better in HQS(16w).Based on our findings,HQS has good therapeutic implications on cardiomyopathy and skeletal muscle with diabetes mellitus.ConclusionsHQS can remarkablly ameliorate the type 2 diabetes mellitus(T2DM),especially the levels of FBG,TC,TG,LDL-C;there was proper decrease in PKC of myocardium and skeletal muscle tissue and HQS has different degrees improvement of MG53,IR,IRS-1,GLUT4 protein expression,it is concluded that HQS improve cardiomyopathy and skeletal muscle with diabetes mellitus by regulating the pathway of MG53/IR、IRS-1.HQS has different degrees reduction of FFA、DAG、ceramide contents,there was remarkable down-regulation of MG53、PPAR-a mRNA,We conclude that HQS ameliorate cardiomyopathy and skeletal muscle with diabetes mellitus by regulating the pathway of MG53/PPAR-α.HQS can significantly reduce the level of Hcy,but the CBS、CTH、MTHFR protein expression has no significant change,so there is possibility that HQS has non-responsive inhibition of CBS,CTH and MTHFR enzymes in the myocardium that leads to cardiomyopathy.Moreover,HQS can improve diabetic model rats of metabolism and skeletal muscle in pathology and reducing the number of myocardial cell apoptosis.In conclusion,HQS has therapeutic implications on cardiomyopathy and skeletal muscle with diabetes mellitus,from the comparison of the overall effect,HQS has more obvious effect on short model,the results revealed that HQS can effectively reduce the weight,blood glucose,blood lipid content,improve the pathological morphology of myocardium and skeletal muscle tissue,regulate the key indicators of PKC、FFA、DAG、ceramide content,at the molecular level,MG53、PPAR-α、IR、IRS-1 were determined,it is concluded that MG53 protein plays important role in the therapeutic implications of HQS on cardiomyopathy and skeletal muscle with diabetes mellitus,HQS can effectively inhibit the pathway of MG53/IR and MG53/PPAR-α.