摘要
Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ 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 Ca^2＋ concentration and sarco-endoplasmic reticulum ATPase 2a（SERCA2a） activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2＋ 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 Ca^2＋ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2＋ level. QSG prevented defective Ca^2＋ 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 Ca^2＋ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion：QSG restored SR Ca^2＋cycling in HF rats and served as an ideal alternative drug for treating HF.
Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ 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 Ca^2＋ concentration and sarco-endoplasmic reticulum ATPase 2a（SERCA2a） activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2＋ 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 Ca^2＋ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2＋ level. QSG prevented defective Ca^2＋ 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 Ca^2＋ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion：QSG restored SR Ca^2＋cycling in HF rats and served as an ideal alternative drug for treating HF.
基金
Supported by the National Natural Science Foundation of China(No.81530100,81470191,and 81302908)
