Abstract: To investigate the effects of hydrogen sulfide (H₂S) on myocardial injury in septic rats and the role of the NOD-like receptor family pyrin domain containing 3/gasdermin D (NLRP3/GSDMD) signaling pathway, a sepsis-induced myocardial injury model was established using cecal ligation and puncture (CLP). The rats were randomly assigned to sham-operated (Sham) group , the CLP group, and the CLP + NaHS group (n = 12). Echocardiography was utilized to assess the left ventricular function of the rats. HE staining and transmission electron microscopy were employed to observe the alterations in myocardial tissue and mitochondria. The levels of plasma inflammatory factors in rats were measured using ELISA. Myocardial enzyme levels and oxidative stress levels in various experimental rat groups were determined using myocardial enzyme assay kits. Western blot analysis was performed to detect the expressions of IL-1β, Caspase-1, and the key pyroptosis proteins NLRP3 and GSDMD in rat myocardial tissue. TUNEL staining was used to observe the apoptosis of rat cardiomyocytes. The results demonstrated that, compared with the Sham group, in the CLP group, the systolic and diastolic functions of the rat hearts were weakened. The myocardial tissue exhibited a disorderly arrangement, with obvious infiltration of inflammatory cells. Mitochondria were found to be smaller with membrane rupture. The levels of inflammatory factors increased, the release of myocardial enzymes augmented, the activity of glutathione (GSH) decreased, and the level of malondialdehyde (MDA) increased. The expressions of IL-1β, Caspase-1, NLRP3, and GSDMD in myocardial tissue were all upregulated, and the apoptosis rate of cardiomyocytes increased.In contrast, compared with the CLP group, in the CLP + NaHS group, the cardiac dysfunction of rats was alleviated, myocardial morphology improved, mitochondrial damage lessened, the levels of inflammatory factors and myocardial enzymes decreased, the levels of oxidative stress markers declined, the activity of GSH increased, the expressions of pyroptosis proteins NLRP3 and GSDMD in myocardial tissue were downregulated, and the apoptosis rate of cardiomyocytes decreased.These results suggest that H₂S may mitigate the inflammatory response and oxidative stress levels by regulating the NLRP3/GSDMD-mediated pyroptosis pathway, thereby improving myocardial injury in septic rats.

Key words: sepsis, myocardial injury, hydrogen sulfide, pyroptosis