Salvianolic Acid B Ameliorates Cardiac Hypertrophy In T2DM Mice By Activating PPAR?

Background:In recent years,the incidence of type 2 diabetes(T2DM)has increased explosively,which has accounted for more than 90%of the prevalence of diabetes mellitus(DM).About 2/3 patients died of cardiovascular diseases,which has become one of the global public health problems.As one of the complications,diabetic cardiomyopathy is the main cause of heart failure,with pathological changes such as hypertrophy,cell apoptosis and interstitial fibrosis.Myocardial hypertrophy has a close relationship with PPAR?,which is the key transcriptional regulator of lipid metabolism,what's more,it is also related to the key enzymes of fatty acid beta and omega oxidation.As is known to all,fatty acids oxidation are the major energy supplying materials of myocardial cells.Therefore,it is significantly important to find the pathogenesis,molecular mechanisms about this disease.In recent years,with the development of health service,traditional Chinese medicine has been widely used in clinic.Salvianolic acid B(SaI B),which is extracted from Salvia miltiorrhiza,plays an important role in the prevention and treatment of cardiovascular and cerebrovascular diseases.lt has been proved that salvianolic acid B can scavenge oxygen free radical and affect the activity of Na-K-ATP enzyme.Its anti-lipid peroxidation is 1000 times than vitamin E,which is one of the most natural antioxidants.Whether it can improve myocardial injury or not,or the regulation of type 2 diabetes,through what mechanisms has not been clearly reported.In this study,we proposed the hypothesis that salvianolic acid B can protect myocardial hypertrophy intype 2 diabetes,and its mechanism is related to PPARa.Objective:1.To investigate the protective role of Salvianolic Acid B(Sal B)on the cardiac hypertrophy in type 2 diabetes mice and high glucose and high insulin induced cardiomyocytes hypertrophy.2.To explore its possible influence on peroxisome proliferator activated receptors-a(PPARa).Methods:The type 2 diabetes mice model were established by high fat diets feeding and streptozotocin(STZ)intraperitoneal injection.The animals were randomly divided into 4 groups:control,T2DM,T2DM+SalB(100mg/Kg-d)and Sal B(100mg/Kg-d).Control group and Sal B group were fed with normal diet,T2DM group and T2DM+Sal B group were fed with high fat and high sugar diet,Sal B treatment group mice were fed with Sal B(100mg/kg)for 8 weeks.Physiological indexes(such as body weight,blood glucose,heart weight),Intraperitoneal glucose tolerance(IPGTT),cross section area of heart,protein expression of PPARa in heart tissue were recorded.LDH assay was applied to test the cytotoxicity of Sal B to cultured neonatal rat cardiomyocytes(NRCM).High glucose and high insulin(HGI)were used to induce hypertrophic growth in NRCM.And cell surface area,3H-Leucine incorporation,3H-D-glucose uptake and PPARa protein level were measured to observe the effect of Sal B and MK886,a PPAR? inhibitor.Results:1.In T2DM model mice,Sal B could lower heart weight,blood glucose level and heart cross section area,while glucose tolerance and PPARa protein level in heart were improved.2.In cultured cardiomyocytes,Sal B(10-100?M)ameliorated the increased levels of cell surface area,3H-Leucine incorporation and improved the decreased 3H-D-glucose uptake and PPARa expression induced by HGI.But those function could be abolished by MK886.Conclusion:Sal B ameliorates cardiac hypertrophy in T2DM mice.This effect may be related to its action on PPARa activation and improved insulin resistance.