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.
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.
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.
QSG restored SR Ca2+ cycling in HF rats and served as an ideal alternative drug for treating HF.
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We would like to thank Prof. WU Yan and Ms. YUAN Yue-ying (Center of Scientific Experiment, Beijing University of Chinese Medicine) for the guidance on echocardiography.
Supported by the National Natural Science Foundation of China (No. 81530100, 81470191, and 81302908)
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Lu, L., Li, C., Wang, Q. et al. Cardioprotective effects of Qishen Granule (芪参颗粒) on sarcoplasmic reticulum Ca2+ handling in heart failure rats. Chin. J. Integr. Med. 23, 510–517 (2017). https://doi.org/10.1007/s11655-017-2809-x
- Qishen Granule
- Ca2+ handling
- heart failure
- ryanodine receptor 2
- sarco-endoplasmic reticulum ATPase 2a
- Chinese medicine