Mechanisms of Hydromorphone-Mediated Protection Against Myocardial Ischemia-Reperfusion Injury via NLRP3 Inflammasome Inhibition.

Myocardial ischaemia/reperfusion, MI/R injury causes significant cardiac damage, leading to disability and mortality. Although hydromorphone attenuates MI/R injury in rat models, its underlying mechanisms remain unclear. This study aimed to investigate the protective effects of hydromorphone against MI/R injury and elucidate its mechanisms. A rat MIRI model was established by occluding the left coronary artery for 30 minutes followed by reperfusion for 120 minutes. Infarct size and cardiac function were assessed using hematoxylin-eosin, HE and Masson's staining. An in vitro model was established using H9C2 cells subjected to hypoxia/reoxygenation, and levels of cellular pyroptosis and pyroptosis-related proteins were quantified. Hydromorphone significantly improved cardiac function in MIRI rats. Pre- and post-treatment with hydromorphone significantly improved cardiomyocyte morphology in MIRI rats. In addition, compared with the model group (IR), the hydromorphone-treated groups (HH+IR, IR+HH) significantly reduced the rna expression of NLRP3, ASC, caspase-1, IL-1β, and IL-18, as well as the protein levels of IL-1β, IL-18. In addition, transmission electron microscopy showed that hydromorphone attenuated CoCl2-induced cardiomyocyte injury. Pre- or post-treatment with hydromorphone exerts protective effects against MIRI by suppressing NLRP3 inflammasomes, potentially providing a theoretical basis for its use as a therapeutic agent in MIRI patients.