Therapeutic effect of Fuzheng Yixin decoction on cardiac insufficiencythe soluble guanylyl cyclase-cyclic guanosine monophosphate-protein kinase G pathway in a doxorubicin-induced dilated cardiomyopathy rat model.

OBJECTIVE: To investigate the effect of Fuzheng Yixin decoction (, FZYX) and explore its underlying mechanisms in doxorubicin-induced dilated cardiomyopathy (DCM) rat model. METHODS: Sprague-Dawley rats were intraperitoneally injected with doxorubicin for 6 consecutive weeks. Ultra-high-perform ance liquid chromatography Q-exactive mass spectrometry was utilized to obtain mass spectrum data for FZYX. The rats were then intragastrically injected with low-dose FZYX, high-dose FZYX, or captopril for 4 weeks. Serum N-terminal pro-brain natriuretic peptide, transthoracic echocardiography, haematoxylin and eosin and Masson staining, electron microscopy, and immunohistochemistry were used to evaluate the efficacy of FZYX. Differentially expressed genes and metabolites in the myocardial tissue of DCM rats following FZYX intervention were subsequently identified through transcriptomics and non-targeted metabolomics. Finally, the influence of FZYX on the expression of natriuretic peptide precursor A (Nppa), natriuretic peptide precursor B (Nppb), soluble guanylyl cyclase (sGC), protein kinase G (PKG), and PKG-1α in DCM rats was verified through quantitative polymerase chain reaction (qPCR), Western blotting (WB) based on the results of transcriptomics and non-targeted metabolomics analyses. RESULTS: FZYX alleviated body weight loss; inhibited ventricular dilatation; restored impaired heart function, ruptured sarcomeres and mitochondrial damage, and pathological changes; and reduced collagen deposition. Transcriptomic and non-targeted metabolomic results revealed that FZYX regulated the expression of sGC-cyclic guanosine monophosphate (cGMP)-PKG pathway-related genes (Nppa, Nppb) and metabolites such as cGMP, 5'-guanylic acid, adenosine. qPCR and WB demonstrated that FZYX suppressed the expression of Nppa and Nppb and increased the expression of sGC, which led to a further increase in the level of PKG and PKG-1α. CONCLUSION: These findings suggest that the cardioprotective effect of FZYX may be mediated through the restoration of the sGC-cGMP-PKG signaling pathway. FZYX may provide a new strategy for clinical application against DCM.