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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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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 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+ 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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Acknowledgements

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.

Author information

Correspondence to Wei Wang.

Additional information

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

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Keywords

  • Qishen Granule
  • Ca2+ handling
  • heart failure
  • ryanodine receptor 2
  • sarco-endoplasmic reticulum ATPase 2a
  • Chinese medicine