Experimental Research on the Anti-Myocardial Fibrosis Effects of Tanshinone IIA

Objective:To study the effects of tanshinoneⅡA(TSN) on signal transduction of transforming growth factor β1(TGFβ1) in cardiac fibroblasts(CF) of rats so as to investigate its mechanism in prevention of myocardial fibrosis.Methods: CF of newborn Sprague-Dawley(SD) rats were isolated by trypsin digestion and differential adhesion method,stimulated with 5ng/mL TGFβ1 and pretreated with 10-6,10-5,10-4mol/L TSN respectively.The mRNA level of fibronectin(FN) was determined with RT-PCR.The protein expression of FN and Smads were detected with western blot.Results: TGFβ1 induced the expression of FN and Smads in a time-dependent manner.Compared with pro-stimulation,the FN mRNA and protein levels increased by 1.3 times and 1.8 times respectively(P0.01,P0.01),the protein expression of phosphorylated Smad2/3(p-Smad2/3) increased by 3.9 times at the end of TGFβ1 stimulation(P0.01).TSN preconditioning down-regulated FN and p-Smad2/3 expression in a dose-dependent manner.10-6mol/L TSN preconditioning had no effect on FN and p-Smad2/3 expression(P0.05,P0.05).After pretreated with 10-5 and 10-4mol/L TSN,the FN mRNA levels decreased by 32.7% and 42.9%(P0.05,P0.01),the FN protein levels decreased by 45.8% and 57.1%(P0.01,P0.01),and the p-Smad2/3 protein expression decreased by 40.5% and 55.4% respectively(P0.05,P0.01).Conclusion: TSN can block TGFβ1/Smads signaling pathway in CF by inhibiting TGFβ1-induced Smad2/3 phosphorylation to prevent myocardial fibrosis.