Abstract

Objective To evaluate the protective effect of Qingxin Jieyu Granule (QXJYG) on myocardial ischemia/reperfusion (I/R) injury by inhibiting cardiomyocyte pyroptosis via circulating exosomes. Methods Seventy-five Wistar rats were randomly assigned to 5 groups using a random number table (15 rats per group): sham-operated, model, low-, medium-, and high-dose QXJYG groups (L-QXJYG, M-QXJYG, and H-QXJYG). The L-QXJYG, M-QXJYG, and H-QXJYG groups were administered QXJYG at doses of 2.87, 5.73, and 11.46 g/kg, respectively, twice daily via intragastric administration for 28 consecutive days. The model group received an equal volume of normal saline following the same schedule. Following 28 days of administration, myocardial I/R injury was induced 1 h after the final dose. Myocardial infarction size, histopathological changes, and expression of key pyroptosis-related molecules in cardiac tissue were assessed. An oxygen-glucose deprivation/reperfusion model using H9c2 cardiomyocytes was established to investigate the cardioprotective mechanism of QXJYG, emphasizing the role of circulating exosomes in modulating pyroptosis through evaluations of cell viability, pyroptotic morphology, and associated molecular expression. Results In vivo experiments demonstrated that QXJYG significantly reduced myocardial infarction size, improved histopathological morphology, suppressed the inflammatory response, and inhibited myocardial pyroptosis (all P <0.05). In vitro , QXJYG was shown to enhance H9c2 cardiomyocyte viability, attenuate inflammation, and suppress pyroptosis by inhibiting the NLRP3/Caspase-1/GSDMD pathway via circulating exosomes (all P <0.05). Conclusion QXJYG alleviates myocardial I/R injury by inhibiting cardiomyocyte pyroptosis through circulating exosomes, potentially via modulation of the NLRP3/ Caspase-1/GSDMD pathway.