Effect of Yixinshu Capsules on calcium regulatory protein in cardiac myocytes of rats with heart failure

Abstract

To explore the molecular mechanism of Yixinshu Capsules(YXS) in restoring cardiac function in rats with heart failure(HF) from the perspective of calmodulin in cardiac myocytes on the basis of determining the therapeutic effect of YXS on HF. The SD rats were subjected to the surgery of ligating the anterior descending branch of the left coronary artery for 4 weeks to established myocardial ischemia-induced heart failure animal model. Then the rats were randomly divided into Sham operation group(Sham, saline), model group(HF, saline), high dose YXS group(HF+YXS-H, 1 600 mg·kg~(-1)·d~(-1)), low dose YXS group(HF+YXS-L, 800 mg·kg~(-1)·d~(-1)) and positive drug valsartan group(HF+VST, 8 mg·kg~(-1)·d~(-1)). After continuous intragastric administration for 6 weeks, the rats were sacrificed and myocardial tissue was collected. Real time quantitative polymerase chain reaction(RT-PCR) and Western blot were used to detect the expression of genes and proteins related to calcium regulation in cardiomyocytes. RESULTS:: showed that as compared with the model group, YXS increased the transcription level of Atp2 a2, Ryr2, CACNA1 C and PRKACA, and increased the expression levels of P-Ryr2, CACNA1 C and SERCA2 a, while decreased the level of NCX1.On the other hand, YXS treatment significantly decreased the RIP3 level and the phosphorylation of its substrate CaMKⅡ protein, and enhanced the phosphorylation expression of PLB. In summary, YXS therapy could regulate the expression of genes and proteins related to calcium regulation in cardiomyocytes, decrease RIP3 and the phosphorylation of CaMKⅡ protein, increase the phosphorylation of PLB at Ser16, and increase the expression of SERCA2 a protein, suggesting that YXS may regulate myocardial calcium homeostasis through CaMKⅡ/PLB/SERCA2 a pathway, to improve the ability of calcium uptake in sarcoplasmic reticulum and stabilize intracellular free Ca~(2+), so as to improve the cardiac function in rats with heart failure. Our study revealed the possible mechanism of YXS in the treatment of heart failure, especially from the perspective of intervention of calmodulin, promoting the clinical application of YXS.