Effects of genistein on myocardial fibrosis in a rat model of type 2 diabetes mellitus via TGF-β1/Smad3 signaling pathway
AIM To explore the effects of genistein on reducing myocardial fibrosis in diabetic rats and the possible mechanism.METHODS The rat models of type 2 diabetes mellitus(T2DM)established by high-fat diet feeding and intraperitoneal streptozotocin(STZ)injection were randomly divided into the model group,the metformin group(100 mg/kg)and the low-dose and high-dose genistein groups(50,100 mg/kg),in contrast to those of the normal group given normal diet,with 10 rats in each group.After 8 weeks gavage of the corresponding drugs,the rats had detections of their weight of the body and the heart,the heart function,levels of the cardiac indices,the biomarkers of serum creatine kinase isoenzyme(CK-MB),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH)activities,the extent of myocardial fibrosis,myocardial mRNA and protein expressions of transforming growth factor-β1(TGF-β1)and Smad homologue 3(Smad 3),and the myocardial distribution and expressions of Collagen Ⅰ and Collagen Ⅲ.RESULTS Compared with the model group,the genistein groups shared increased body weight,stroke output(SV)and ejection fraction(EF)(P<0.01);decreased levels of cardiac indices,left ventricular internal diameter end systole(LVIDs),CK-MB,AST and LDH activities(P<0.05,P<0.01);decreased relative area and myocardial expressions of CollagenⅠand CollagenⅢ(P<0.05,P<0.01);and decreased myocardial expressions of TGF-β1 and Smad3 mRNA and protein(P<0.05,P<0.01).Additionally,the high-dose genistein group was observed with decreased level of left ventricular internal diameter end-diastole(LVIDd)(P<0.05).CONCLUSION Genistein can protect the hearts of T2DM rat models by reducing their myocardial fibrosis via TGF-β1/Smad3 signaling pathway.
万方数据
维普
