Cardio-Protective effects of Qishen Granule (芪参颗粒) on sarcoplasmic reticulum Ca 2+ handling in heart failure rats

Abstract

Objectives

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 specifific 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.

Conclusions

QSG restored SR Ca²⁺ cycling in HF rats and served as an ideal alternative drug for treating HF.

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