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

XIANG Chang-pei1,2 ZHOU Rui1,2 ZHANG Jing-jing2 YANG Hong-jun1,2

(1.College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China 650500)
(2.Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China 100700)

【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 in the context of the therapeutic effect of YXS on HF. The SD rats were subjected to the ligation of the anterior descending branch of the left coronary artery for four weeks to establish myocardial ischemia-induced HF animal model. The rats were randomly assigned into a sham operation group (Sham, saline), a model group (HF, saline), a high dose YXS group (HF + YXS-H, 1 600 mg·kg−1·d−1), a 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 six weeks, the rats were sacrificed and myocardial tissues were 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 cardiac myocytes. Results showed that compared with the model group, YXS increased the transcription levels of Atp2a2, Ryr2, CACNA1C, and PRKACA, and increased the expression levels of p-Ryr2, CACNA1C, and SERCA2a, while decreased the level of NCX1. On the other hand, YXS medication significantly decreased the RIP3 level and the phosphorylation of its substrate CaMKⅡ protein, and enhanced the phosphorylation expression of PLB. In summary, YXS medication could regulate the expression of genes and proteins related to calcium regulation in cardiac myocytes, inhibit RIP3 and the phosphorylation of CaMKⅡ protein, promote the phosphorylation of PLB at Ser16, and increase the expression of SERCA2a protein, suggesting that YXS may regulate myocardial calcium homeostasis through CaMKⅡ/PLB/SERCA2a pathway to improve the ability of calcium uptake in sarcoplasmic reticulum and stabilize intracellular free Ca2+, so as to improve the cardiac function in rats with HF. This study revealed the possible mechanism of YXS in the treatment of HF, especially from the intervention of calmodulin, promoting the clinical application of YXS.

【Keywords】 heart failure; Yixinshu Capsules; calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ); sarcoplasmic reticulum calcium adenodine triphosphatase 2a (SERCA2a);

【DOI】

【Funds】 National Natural Science Foundation of China (81603422, 81974550)

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This Article

ISSN:1001-5302

CN: 11-2272/R

Vol 45, No. 20, Pages 4984-4990

October 2020

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  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References