摘要

Objective:To assess the effects of Qishen Granule(芪参颗粒, QSG) on sarcoplasmic reticulum(SR) Ca2+ handling in heart failure(HF) model of rats and to explore the underlying molecular mechanisms. Methods:HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham(n=10), model(n=10), QSG(n=12, 2.2 g/kg daily) and metoprolol groups(n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca2+ concentration and sarco-endoplasmic reticulum ATPase 2a(SERCA2a) activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca2+ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results:HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca2+ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca2+ level. QSG prevented defective Ca2+ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca2+ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion:QSG restored SR Ca2+cycling in HF rats and served as an ideal alternative drug for treating HF.