Zhongguo Zhong Yao Za Zhi. 2026 Aug;51(15):4475-4483. doi: 10.19540/j.cnki.cjcmm.20260414.702.
ABSTRACT
This study aimed to explore whether Tongmai Yangxin Pills(TMYX) can improve cardiac arrhythmia in rats after ischemia-reperfusion(I/R) by inhibiting inflammation and apoptosis through the advanced glycation end products(AGE)-receptor for AGE(RAGE) signaling pathway. This study employed the Langendorff isolated heart perfusion system for electrophysiological mapping to determine the safe concentration range of TMYX. Subsequently, network pharmacology was utilized to predict the potential targets and key signaling pathways of TMYX against cardiac arrhythmia. Finally, the in vivo I/R cardiac arrhythmia model in rats was established through left anterior descending coronary artery ligation for verification. In the in vitro experiment, the control group and the TMYX group were used to explore the safe concentration of TMYX, and the I/R group and the TMYX group were used to observe the incidence of cardiac arrhythmia. The animals for the in vivo experiment were randomly divided into the control, I/R, low/high-dose TMYX, metoprolol, and RAGE inhibitor FPS-ZM1 groups, and corresponding interventions were given. During the experiment, cardiac arrhythmia was monitored by electrocardiograms, and cardiac function was evaluated by echocardiograms. The myocardial infarction area was observed by triphenyltetrazolium chloride(TTC) staining, aggregation of inflammatory cells was observed by hematoxylin-eosin(HE) staining, and cell apoptosis was detected by TUNEL staining. The levels of inflammatory factors were determined by enzyme-linked immunosorbent assay(ELISA). Network pharmacology was used to find the potential targets and key signaling pathways of TMYX, and the changes in the expression levels of related proteins were detected by Western blot. When the dose did not exceed the clinical equivalent dose(5 mg·mL~(-1)), TMYX had little effect on the electrophysiological parameters of isolated hearts of rats. TMYX could significantly improve the cardiac arrhythmia induced by I/R injury in in vivo and isolated hearts, reduce the incidence and duration of ventricular premature beats, ventricular tachycardia, and ventricular fibrillation, and improve left ventricular systolic function. TMYX treatment could reduce the myocardial infarction area, attenuate the aggregation of inflammatory cells in myocardial tissue, lower the level of cell apoptosis, and down-regulate the abnormal increase in the expression of serum interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the same time, it was observed that TMYX treatment could inhibit the activation of the AGE-RAGE signaling pathway in I/R myocardial tissue and the changes in the protein expression of B-cell lymphoma-2(Bcl-2) and Bcl-2 associated X protein(Bax). This study, through the integration of experimental strategies, has for the first time confirmed TMYX may inhibit the activation of the AGE-RAGE signaling pathway in I/R myocardial tissue of rats, thereby reducing inflammation and apoptosis, and ultimately improving I/R cardiac arrhythmia.
PMID:42693062 | DOI:10.19540/j.cnki.cjcmm.20260414.702