Rutin Protects Myocardial Ischemia–Reperfusion Injury via the NF-κB/NLRP3/Pyroptosis Pathway

This study aimed to determine the protective role and mechanism of rutin on myocardial ischemia-reperfusion (I/R) injury. First, a myocardial I/R injury model was established and subjected to ischemia and hypoxia to simulate the model of I/R injury in vivo. Triphenyltetrazolium chloride was used to determine the myocardial infarct area. Immunohistochemistry, the TUNEL assay, and hematoxylin and eosin staining were performed to determine NLRP3 expression, myocardial cell apoptosis, and cardiomyocyte morphology, respectively. Western blot analysis, the CCK-8 assay, and an ELISA were used to determine pyroptosis-associated protein expression, cell viability, and inflammatory factor expression, respectively. Rutin was shown to reduce the myocardial infarct area and myocardial cell apoptosis in vivo. Furthermore, rutin reduced the CK-MB, cTnT/I, and malondialdehyde levels after I/R injury. NLRP3 expression was downregulated after treatment with rutin compared to the sham group. NF-κB, NLRP3, cleaved caspase-1, and cleaved gasdermin D protein were also downregulated after rutin treatment. Rutin treatment enhanced cell viability after hypoxia-reperfusion conditions in <i>in vitro</i> experiments, reduced cell apoptosis, and reduced the LDH and ROS levels. Rutin also downregulated the expression of inflammatory factors (IL-1β, TNF-α, and IL-18) and pyroptosis-related proteins (NF-κB, NLRP3, cleaved caspase-1, and cleaved gasdermin D). Moreover, the protective effect of rutin on myocardial I/R injury disappeared after the NLRP3 agonist, nigericin, combined with rutin. These findings indicated that rutin protected myocardial I/R injury via the NF-κB/NLRP3/pyroptosis pathway and suggested a new treatment approach for myocardial I/R injury.