Qishen granules exerts cardioprotective effects on rats with heart failure via regulating fatty acid and glucose metabolism

BACKGROUND: Qishen granules (QSG) has been applied to treat heart failure (HF) for decades. Our previous transcriptomics study has suggested that Qishen granules (QSG) could regulate the pathways of cardiac energy metabolism in HF, but the specific regulatory mechanism has not yet been clarified. This study was to investigate the potential mechanism of QSG in regulating myocardial fatty acid (FA) and glucose metabolism in a rat model of HF. METHODS: The model of HF was induced by left anterior descending coronary artery ligation. Cardiac structure and function were assessed by cine magnetic resonance imaging (MRI) and echocardiography. Level of glucose metabolism was non-invasively evaluated by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Blood lipid levels were determined by enzymatic analysis. The mitochondrial ultrastructure was observed with a transmission electron microscope. The critical proteins related to FA metabolism, glucose metabolism and mitochondrial function were measured by western blotting. The ANOVA followed by a Fisher’s LSD test was used for within-group comparisons. RESULTS: QSG ameliorated cardiac functions and attenuated myocardial remodeling in HF model. The levels of serum TC, TG and LDL-C were significantly reduced by QSG. The proteins mediating FA uptake, transportation into mitochondria and β-oxidation (FAT/CD36, CPT1A, ACADL, ACADM, ACAA2 and SCP2) as well as the upstreaming transcriptional regulators of FA metabolism (PPARα, RXRα, RXRβ and RXRγ) were up-regulated by QSG. As to glucose metabolism, QSG inhibited glycolytic activity by decreasing LDHA, while stimulated glucose oxidation by decreasing PDK4. Furthermore, QSG could facilitate tricarboxylic acid cycle, promote the transportation of ATP from mitochondria to cytoplasm and restore the mitochondrial function by increasing SUCLA2, CKMT2 and PGC-1α and decreasing UCP2 simultaneously. CONCLUSION: QSG improved myocardial energy metabolism through increasing FA metabolism,inhibiting uncoupling of glycolysis from glucose oxidation.