Calcium/calmodulin-dependent protein kinase II (CaMKII) is critical for regulating cardiac electrophysiological functions. Research has shown that Yangxin Dingji capsule (YXDJ) significantly inhibits ventricular arrhythmia (VA). However, it is unclear whether YXDJ inhibits VA by regulating CaMKII. The aim of the present study was to elucidate the effects of YXDJ on the expression of CaMKII and sarco/endoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) and clarify the molecular mechanism by which YXDJ inhibits VA. Sixty healthy Sprague‒Dawley rats were randomly divided into control, model, Propranolol, and YXDJ low-, medium- and high-dose groups and administered the corresponding treatment. The VA model was constructed by the isoproterenol hydrochloride (ISO) “6+1” method. Changes in the electrocardiograms of the rats were recorded, and pathomorphological changes were observed via hematoxylin‒eosin staining. Enzyme-linked immunosorbent assays were used to measure cardiac troponin I, tumor necrosis factor-α, interleukin-1β, interleukin-6, and myocardial Ca²⁺ levels and CaMKII activity. An automatic biochemical analyzer was used to measure the malondialdehyde, nitric oxide, and reduced glutathione levels and superoxide dismutase activity. Quantitative real-time polymerase chain reaction (PCR) was performed to detect SERCA2 and CaMKII gene expression, whereas the expression of CaMKII, phosphorylated phospholamban (P-PLB) and SERCA2 was evaluated via Western blotting. YXDJ was found to improve cardiac hypertrophy, reduce the incidence of VA, and protect cardiac tissue by alleviating inflammation and reducing oxidative stress levels in the body. The ISO-induced increases in CaMKII activity, CaMKII mRNA and protein expression, P-PLB protein expression and Ca²⁺ levels and decreases in SERCA2 mRNA and protein expression were effectively counteracted by YXDJ. YXDJ alleviated VA by reducing CaMKII expression and activating SERCA2, thereby reducing the Ca²⁺ load.

Kexin Ma, Guoping Ma, Zan Xie, Mian Li, Ruijing Liang, Zijing Guo, Yameng Feng, Wenjie Liang, Qiuhong Guo. The Mechanism of Isoproterenol Hydrochloride-Induced Cardiac Arrhythmia and How Yangxin Dingji Capsule Alleviates These Effects by Modulating the CaMKII Pathway . Frontiers in Medical Science Research (2025), Vol. 7, Issue 1: 17-33. https://doi.org/10.25236/FMSR.2025.070104.

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