The Protective Effects Of Isosteviol Sodium On Myocardial Hypertrophy In Transverse Aortic Constriction Rats

Pathological myocardial hypertrophy and remodeling is a common complication of a variety of heart disease, ultimately leading to heart failure. Looking for new drug targets and therapeutic methods for inhibiting and reversing myocardial remodeling has great significance for the prevention and treatment of heart disease. Currently, no effective drugs listed. Early study has shown that natural product isosteviol has protective effect on acute myocardial ischemia. This paper uses a good solubility of isosteviol sodium salt formulation(STVNa) to study whether isosteviol has the protective effect on myocardial hypertrophy and remodeling. The main contents are as follows:Myocardial hypertrophy was induced by transverse aortic constriction(TAC) in rats. The rats were randomly divided into six groups: sham group, TAC group, STVNa low, middle, high-dose treated groups(1, 2 or 8mg/kg/d), sildenafil treated group(70mg/kg/d). After 3 and 9 weeks surgery, rats in each group were anesthetized, using pressure-volume catheter to test cardiac function and measured arterial pressure. Weighing heart weight and calculating the heart weight/body weight ratio. Cardiomyocytes cross-sectional area was measured by hematoxylin-eosin staining. Myocardial fibrosis was measured by picric acid-sirius red staining. The expression of F-actin in myocardial tissue was measured by FITC-phalloidin staining. Meanwhile, the electrocardiogram(ECG) of rats in each group was compared to analyze the effect of STVNa on myocardial ischemia. Acute isolated myocardial cells were used to study the effect of STVNa on calcium transient by confocal microscopy imaging techniques. Cultured myocardial fibroblasts were used to study the inhibiting effect of STVNa on myocardial fibroblast proliferation induced by TGF-β1 and investigate the effects of STVNa on the level of c GMP in myocardial fibroblasts.The results showed that rats appeared myocardial hypertrophy and fibrosis after TAC 3 weeks. Both STVNa and sildenafil could significantly inhibit myocardial hypertrophy and fibrosis. The rats appeared cardiac decompensation after TAC 9 weeks. Both STVNa and sildenafil could significantly improve cardiac function, and inhibit fibrosis and the expression of myocardial F-actin. Besides, STVNa also had improvement for myocardial ischemia. In the above results, the effects of STVNa improving cardiac funtion and myocardial ischemia and inhibiting fibrosis were significantly superior to sildenafil. In cultured fibroblasts, STVNa could significantly inhibit TGF-β1 induced cell proliferation and increase the level of c GMP in myocardial fibroblasts. In the acute isolated myocardial cells, STVNa had no significant effect on the baseline level of intracellular Ca2+ and Ca2+ transient. Analysis of these results, the mechanism of STVNa inhibiting fibrosis may be through the c GMP-PKG signal channel reverse the collagen gene expression induced by TGF-β1.Conclusion: This study was first demonstrated STVNa could inhibit myocardial fibrosis and remodeling as well as improve cardiac function in hypertrophy myocardium. Sildenafil was an experimental drug used to anti-myocardial hypertrophy in clinical. This study showed that the effect of STVNa was significantly superior to sildenafil. It could be a novel drug to anti-myocardial hypertrophy and prevent heart failure.