Author + information
- 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine
- 2Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine
- 3School of Life Sciences, Beijing University of Chinese Medicine
- 4School of Chinese Materia Medica, Beijing University of Chinese Medicine
To assess the effect of Qishen Granule (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 divided into sham, model, QSG and positive control groups. 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 mediators in SR Ca2+ handling were evaluated by western-blot and RT-qPCR.
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-regulated transcriptional expression of 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.