Abstract
QiShenYiQi dripping pills (QSYQ), a traditional Chinese medicine, are commonly used to treat coronary heart disease, and QSYQ was recently approved as a complementary treatment for ischemic heart failure in China. However, only few studies reported on whether QSYQ exerts a protective effect on heart failure induced by pressure overload. In this study, we explored the role of QSYQ in a mouse model of heart failure induced by transverse aortic constriction (TAC). Twenty-eight C57BL/6J mice were divided into four groups: Sham + NS group, Sham + QSYQ group, TAC + NS group, and TAC + QSYQ group. QSYQ dissolved in normal saline (NS) was administered intragastrically (3.5 mg/100 g/day) in the Sham + QSYQ and TAC + QSYQ groups. In the Sham + NS and TAC + NS groups, NS was provided every day intragastrically. Eight weeks after TAC, echocardiography, and cardiac catheterization were performed to evaluate the cardiac function, and immunofluorescent staining with anti-actinin2 antibody was performed to determine the structure of the myocardial fibers. Moreover, TUNEL staining and Masson trichrome staining were employed to assess the effects of QSYQ on cardiac apoptosis and cardiac fibrosis. Western blots and real-time polymerase chain reaction (PCR) were used to measure the expression levels of vascular endothelial growth factor (VEGF) in the heart, and immunohistochemical staining with anti-CD31 antibody was performed to explore the role of QSYQ in cardiac angiogenesis. Results showed that TAC-induced cardiac dysfunction and disrupted structure of myocardial fibers significantly improved after QSYQ treatment. Moreover, QSYQ treatment also significantly improved cardiac apoptosis and cardiac fibrosis in TAC-induced heart failure, which was accompanied by an increase in VEGF expression levels and maintenance of microvessel density in the heart. In conclusion, QSYQ exerts a protective effect on TAC-induced heart failure, which could be attributed to enhanced cardiac angiogenesis, which is closely related to QSYQ. Thus, QSYQ may be a promising traditional Chinese medicine for the treatment of heart failure induced by pressure overload such as hypertension.
Highlights
QiShenYiQi dripping pills (QSYQ) is a compound Chinese medicine, which is composed of six herbs including 2 star herbs: Astragalus membranaceus (Fisch.) Bunge (“huang-qi” in Chinese) and Salvia Miltiorrhiza Bunge (“danshen” in Chinese), and 4 adjunctive herbs: Lonicera japonica Thunb., Scrophularia aestivalis Griseb., Aconitum fischeri Rchb., and Glycyrrhiza uralensis Fisch (Wang et al, 2017)
After treatment with QSYQ, the Akt activation and endothelial NO synthase (eNOS) phosphorylation was significantly increased in transverse aortic constriction (TAC) + normal saline (NS) group. These results indicated that cardiac vascular endothelial growth factor (VEGF)/Akt/eNOS pathway in the TAC + NS group was strongly suppressed compared with those in the Sham + NS group and the QSYQ was able to induce the activation of cardiac VEGF/Akt/eNOS pathway
Our results showed that treatment with QSYQ could protect against TAC-induced cardiac dysfunction and disrupted myocardial fiber structure
Summary
QiShenYiQi dripping pills (QSYQ) is a compound Chinese medicine, which is composed of six herbs including 2 star herbs: Astragalus membranaceus (Fisch.) Bunge (“huang-qi” in Chinese) and Salvia Miltiorrhiza Bunge (“danshen” in Chinese), and 4 adjunctive herbs: Lonicera japonica Thunb., Scrophularia aestivalis Griseb., Aconitum fischeri Rchb., and Glycyrrhiza uralensis Fisch (Wang et al, 2017). Heart failure is the ultimate result of a large number of cardiovascular diseases, which are a leading causes of morbidity and mortality worldwide (Shah and Mann, 2011). It is regarded as a progressive and irreversible process characterized by cardiac pump failure and cardiac remodeling (Hou and Kang, 2012). Pathological cardiac remodeling, resulting from cardiac pressure, volume overload, or ischemic injury, is considered the most crucial mechanism for the development of heart failure (Ho et al, 2010; Ahmad et al, 2012) and is a progressive and irreversible process characterized by cardiac hypertrophy, cardiac apoptosis, and cardiac fibrosis (Cohn et al, 2000). Preventing or reversing pathological cardiac remodeling is an effective way to prevent heart failure (Kirkpatrick and St John Sutton, 2012)
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