YQWY decoction reverses cardiac hypertrophy induced by TAC through inhibiting GATA4 phosphorylation and MAPKs / 中国天然药物

ABSTRACT

To investigate the effect of Yiqi Wenyang (YQWY) decoction on reversing cardiac hypertrophy induced by the transverse aortic constriction (TAC). Wistar rats aged 7-8 weeks were subjected to TAC surgery and then randomly divided into 4 groups (n = 5/group) Sham group, TAC group, low-dose group and high dose group. After 16-week intragastric administration of YQWY decoction, the effect of YQWY decoction on alleviating cardiomyocyte hypertrophy was examined by transthoracic echocardiography (TTE), hematoxylin/eosin (HE), wheat germ agglutinin (WGA) staining, enzyme linked immunosorbent assay (ELISA), Western blot (WB), immunohistochemistry (IHC) and immunofluorescence (IF), respectively. The results showed significant differences in left ventricle volume-diastole/systole (LV Vol d/s), N-terminal pro-B-type brain natriuretic peptide (NT-proBNP) (P < 0.01), Ejection Fraction (EF), LV mass and fractional shortening (FS) (P < 0.05) between YQWY-treated group and TAC group. HE and WGA staining showed that treatment with YQWY decoction dramatically prevented TAC-induced cardiomycyte hypertrophy. Moreover, the results of WB, IHC and IF indicated that administration of YQWY could suppress the expressions of cardiac hypertrophic markers, which included the atrial natriuretic peptide (ANP), BNP and myosin heavy chain 7 (MYH7) (P < 0.05) and inhibit phosphorylation of GATA binding protein 4 (P-GATA4) (P < 0.05), phosphorylation of extracellular signal-regulated kinase (P-ERK) (P < 0.05), phosphorylation of P38 mitogen activated protein kinase (P-P38) (P < 0.05) and phosphorylation of c-Jun N-terminal kinase (P-JNK) (P < 0.05). Thus, we concluded that YQWY decoction suppressed cardiomyocyte hypertrophy and reversed the impaired heart function, and the curative effects of YQWY decoction were associated with the decreased phosphorylation of GATA4 and mitogen activated protein kinases (MAPKs), as well as the reduced expression of the downstream targets of GATA4, including ANP, BNP, and MYH7.