Effect And Mechanism Of YQWY Prescription On Heart Failure Induced By TAC Pressure Overload

Objective:To investigate the effect and mechanism of the Yiqiwenyang(YQWY)prescription on reversing cardiac hypertrophy induced by the transverse aortic constriction(TAC),and explore the effect of Astragalus and Astrogaloside ?(As?)on the calcium transient and cardiac contractility with heart failure to better understand the effect and mechanism of YQWY prescription and its main component Astragalus?Methods:Wistar Rats aged 7-8 weeks were subjected to TAC surgery and then randomly divided into 4 groups after observation for one week:Sham group(n=5),TAC group(n=5),low-dose group(n=5)and high dose group(n=5).After 16-week intragastric administration of YQWY prescription,the effect of the YQWY prescription on alleviating the cardiac hypertrophy and improving the function were examined by transthoracic echocardiography(TTE),hematoxylin/Eosin(HE),wheat germ agglutinin(WGA)staining,enzyme linked immunosorbent assay(Elisa),Western blot(WB),immunohistochemical(IHC)and immunofluorescence(IF),respectively.Observation the effect of the water decoction of Astragalus(AsWD)and AsIV on the calcium transient and cardiomycyte contraction.Results:The results showed significant differences in LV VoLume-diastolic/systolic,NT-proBNP(P<0.01),Ejection Fraction(EF)and Fraction Shortening(FS)(P<0.05)between YQWY-treated group and TAC group after 16 weeks of intragastric administration.HE and WGA staining showed that treatment with YQWY prescription dramatically prevented TAC-induced cardiac hypertrophy and inhibited expressions of cardiac hypertrophic markers,which included the atrial natriuretic peptide(ANP),B-type brain natriuretic peptide(BNP)and myosin heavy chain S(MHC?/MYH7)(P<0.01).The results of WB,IHC and IF indicated that the high-dose group significantly attenuated the TAC-induced cardiomyocyte hypertrophy through inhibiting P-GATA4(P<0.01),P-ERK(P<0.01),P-P38(P<0.05)and P-JNK(P<0.01).Astragalus and Astragaloside IV can significantly increase the cardiomyocyte sarcomere length(P<0.001),enhance myocardial contractility and normalize the cardiomyocyte beats.Conclusion:Thus,we concluded that YQWY decoction suppressed the cardiomyocyte hypertrophy and reversed the impaired heart function through inhibiting GATA4 phosphorylation and MAPKs signaling pathways.Astragalus and AsIV can restore heart failure-induced changes on calcium transients to enhance the cardiomyocytes contractility to prevent the electrical remodeling.