Flurbiprofen axetil attenuates myocardial ischemia-reperfusion injury and suppresses NLRP3 inflammasome signaling.
TL;DR
Results demonstrated that flurbiprofen axetil significantly alleviated myocardial structural injury and reduced serum levels of CK-MB, LDH, and cTnI, and levels of pro-inflammatory cytokines, including IL-1β, IL-18, and TNF-α, were markedly decreased.
Abstract
Myocardial ischemia-reperfusion (I/R) injury is characterized by excessive inflammatory responses and pyroptosis, a form of regulated cell death in which activation of the NLRP3 inflammasome plays a central role. Despite advances in therapeutic strategies, effective interventions targeting inflammation-driven myocardial injury remain limited. Flurbiprofen axetil, a non-selective cyclooxygenase inhibitor with well-established anti-inflammatory properties, has been widely used in clinical practice; however, its role in myocardial I/R injury and its association with inflammasome-related signaling remain incompletely understood. In this study, we investigated the cardioprotective effects of flurbiprofen axetil in a rat model of myocardial I/R injury. Histological analysis, enzyme-linked immunosorbent assay (ELISA), TdT-mediated dUTP nick-end labeling (TUNEL) staining, and Western blotting were performed to evaluate myocardial structural damage, inflammatory responses, and cardiomyocyte death. Our results demonstrated that flurbiprofen axetil significantly alleviated myocardial structural injury and reduced serum levels of CK-MB, LDH, and cTnI. In addition, levels of pro-inflammatory cytokines, including IL-1β, IL-18, and TNF-α, were markedly decreased. At the molecular level, flurbiprofen axetil treatment was associated with reduced expression of NLRP3, ASC, caspase-1, and GSDMD-N, consistent with attenuation of inflammasome-related and pyroptotic signaling. Furthermore, postconditioning tended to exhibit greater protective effects than preconditioning in attenuating inflammatory responses and myocardial injury markers, whereas both strategies showed comparable effects on cardiomyocyte death. In conclusion, flurbiprofen axetil attenuates myocardial I/R injury, and these cardioprotective effects are associated with attenuation of NLRP3 inflammasome-related and downstream pyroptotic signaling, accompanied by reduced inflammatory responses.