【摘 要】
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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
【机 构】
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School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China;Modern
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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 SERCA2a and promoting phosphorylation of phospholamban.Conclusion:QSG restored SR Ca2+ cycling in HF rats and served as an ideal alternative drug for treating HF.
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