Shenfu Injection Regulates Pyroptosis through the NLRP3/Caspase-1 Pathway to Improve Chronic Heart Failure

Abstract

Objective: The objective of this research is to clarify how Shenfu injection enhances chronic heart failure treatment, specifically by examining its influence on the NLRP3-Caspase-1 pathway. Methods: The chronic heart failure in rats was induced through subcutaneous administration of isoproterenol. The effectiveness of Shenfu injection was assessed by examining cardiac function using echocardiography, monitoring changes in serum N-terminal brain natriuretic peptide levels, and conducting histological analysis with HE and Masson staining to evaluate modifications in myocardial cell structure and fibrosis. To assess the protein levels associated with the NLRP3/Caspase-1 pathway, cellular pyroptosis, and myocardial ultrastructure, various techniques including Western blotting, GSDMD-N staining, TUNEL immunofluorescence dual staining, and electron microscopy were employed. Results: Shenfu injection significantly ameliorated cardiac function, myocardial arrangement, and fibrosis in chronic heart failure rats. Significantly, it substantially decreased the protein levels of NLRP3, caspase-1, IL-1β, and IL-18, along with a reduction in cellular pyroptosis positivity (P < 0.05). Under electron microscopy, the morphology appeared normal, with only partial cell membranes exhibiting pore formation. Conclusion: In summary, our research indicates that the SFI intervention improves cardiac function in the chronic heart failure model induced by isoproterenol, possibly by regulating the NLRP3/Caspase-1 pathway to reduce pyroptosis, suppress inflammatory responses, protect myocardial cells, and maintain the integrity of cellular ultrastructure.