RESUMO
Objective To investigate the protective effects of daidzein (DD) on myocardial hypertrophy and fibrosis induced by pressure overload in rats and to study its mechanism. MethodsMyocardial hypertrophy and fibrosis model of rats induced by pressure overload was prepared by constricting abdominal aorta. The operated rats were randomly divided into sham operated control group, aorta-constricted model group, and three DD groups (30, 60, and 120 mg/kg). Four weeks later, the heart-weight (HW), left ventricular weight (LVW), the ratio of HW/BW and LVW/BW (LVI), and the cardio-myocyte diameters (MD) after dying by HE color were measured. The content of collagen and nitric oxide (NO), the activity of calcineurin (CaN) and Na+, K+-ATPase, Ca2+-ATPase in the left ventricle were quantified with spectrophotometry. The angiotension Ⅱ (AngⅡ) in the left ventricle was messured with radioimmunoassay. Results In aorta-constricted model group, the ratio of HW/BW, LVI, and MD as well as the content of collagen and AngⅡ, the activity of CaN in the left ventricle was significantly increased, and Na+, K+-ATPase, Ca2+-ATPase activity and NO content in the left ventricle were obviously decreased. After treatment of the left ventricular with DD, NO content, Na+, K+-ATPase, Ca2+-ATPase activity were significantly increased, the content of collagen and of AngⅡ and the activity of CaN in the left ventricle and the ratio of HW/BW, LVI, and MD were significantly reduced. ConclusionDD has protective effects on ventricular remodeling in rats with myocardial hypertrophy and fibrosis induced by pressure overload and its mechanism may be related to raising NO content and reducing the level of AngⅡ and the activity of CaN.
RESUMO
Aim To observe effects of Sodium tanshinoneⅡA sulfonate(STS) on angiotensionⅡ(AngⅡ)-induced cardiomyocyte hypertrophy and the expression of phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2). Methods In the primary culture of neonatal rat cardiomyocytes, as indexes of cardiomyocyte hypertrophy, the total protein was determined by coomassie brilliant blue and protein synthesis rate was measured by [3H]-Leucine incorporation. The expression of p-ERK1/2 was assessed using Western blot and fluorescence microscope. Results ① The total protein and protein synthesis rate stimulated by Ang Ⅱ(1 ?mol?L-1)in the cardiomyocytes increased significantly in contrast to that of control; STS could effectively decrease the increased total protein level induced by Ang Ⅱand markedly inhibit synthesis of protein. ② AngⅡ(1 ?mol?L-1) had the effect of promoting activation of ERK1/2 and then appeared in nucleus rapidly. The translocation process of ERK1/2 induced by AngⅡ was blocked distinctly by STS. ③ Cardiomyocyte pretreated with Ang Ⅱ(1 ?mol?L-1)for 5 min, the p-ERK1/2 protein expression began to increase ,the peak effect was at 10 min. While pretreatment with STS(2, 10, 50 ?mol?L-1) ,Ang Ⅱ-induced increase in p-ERK1/2 were inhibited evidently. ④ In pretreatment of cardiomyocyte with STS in different doses for 30 min, STS was found to be able to inhibit the expression of p-ERK1/2 stimulated by AngⅡ in a dose-dependent manner. Conclusions The results suggested that activation of ERK1/2 might play an important role in cardiomyocytes hypertrophy induced by Ang Ⅱ,and the anti-hypertrophic effect of STS on cardiomyocyte hypertrophy induced by AngⅡ might be associated to its inhibitory effect on ERK signaling pathway.
