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| Cardioprotective Effects of Qishen Granule (芪参颗粒) on Sarcoplasmic Reticulum Ca2+ Handling in Heart Failure Rats |
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| KeyWord:Qishen Granule, Ca2+ handling, heart failure, ryanodine receptor 2, sarco-endoplasmic reticulum ATPase 2a, Chinese medicine |
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| Abstract: |
| 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+ release-uptake 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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