Abstract
Objective To observe the effect of Danshensu (DSS) on cardiac function and myocardial fibrosis in pressure-overloaded mice. Methods C57BL/6 male mice were randomly divided into four groups: Sham-Saline, Sham-DSS, TAC-Saline and TAC-DSS. Mice ventricular remodeling model were established by transverse aortic constriction (TAC) operation. One week later, the mice were fed with DSS or Saline for 7 weeks. After echocardiographic evaluation, cardiomyocyte cross-sectional area and myocardial fibrosis were determined by hematoxylin and eosin (HE) and Masson staining, respectively. Western blotting analysis was performed to detect the expression of transforming growth factor-β1 (TGF-β1)/Smad signaling pathway related proteins. Results Compared with Sham-Saline group, the left ventricular ejection fraction and fraction shortening in TAC-Saline group were reduced [(48.19±1.11)% vs. (80.78±1.30)%; (24.36±0.63)% vs. (42.87±1.09)%, P<0.05], which could be improved by DSS [(57.35±1.09)% and (29.88±0.68)%, respectively, P<0.05]. HE staining indicated an enlargement in cardiomyocyte cross-sectional area after TAC [(379±25) μm2 vs. (192±12) μm2,P<0.05], which could be ameliorated by DSS [(264±18) μm2,P<0.05]. Masson staining demonstrated that the degree of myocardial fibrosis was increased following TAC [(11.34±1.43)% vs. (2.18±0.14)%, P<0.05], which could be mitigated by DSS intervention[(5.26±1.17)%, P<0.05]. In addition to a reduction in Smad7 protein content, an increase in the protein level of p-Smad2, p-Smad3 and TGF-β1 were also observed in TAC-Saline group compared to Sham-Saline group (P<0.05); compared with TAC-Saline group, TAC-DSS group showed a reduced expression of p-Smad2, p-Smad3 and TGF-β1 and an increased expression of Smad7 (P<0.05). Conclusion DSS may ameliorate myocardial fibrosis via TGF-β1/Smad signaling pathway, thus improving the cardiac function and ventricular remodeling after pressure overload. Key words: Danshensu; Transverse aortic constriction; transforming growth factor-β1/Smad; Myocardial fibrosis
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