Resveratrol Upregulates miR-124-3p Expression to Target DAPK1, Regulating the NLRP3/Caspase-1/GSDMD Pathway to Inhibit Pyroptosis and Alleviate Spinal Cord Injury

Abstract

Currently, an effective treatment for spinal cord injury (SCI) is not available. Due to the irreversible primary injury associated with SCI, the prevention and treatment of secondary injury are very important. In the secondary injury stage, pyroptosis exacerbates the deterioration of the spinal cord injury, and inhibiting pyroptosis is beneficial for recovery from SCI. The aim of this study was to clarify the role of resveratrol (RES) and the antipyroptotic mechanisms of RES and miR-124-3p in SCI to lay a theoretical foundation for the clinical treatment of SCI and provide new therapeutic approaches. Using cell staining and related molecular protein detection techniques to assess DAPK1, the effects of miR-124-3p and RES on pyroptosis were investigated, and the effects of RES on injured spinal cord repair in rats were evaluated using tissue staining and related functional recovery experiments. In vitro, DAPK1 interacts with NLRP3, exerting a pyroptotic effect through the NLRP3/Caspase-1/GSDMD pathway and DAPK1 knockdown inhibits pyroptosis. miR-124-3P negatively regulates the level of DAPK1 and reduced cell pyroptosis. RES increased miR-124-3p expression and reduces DAPK1 expression, affecting the NLRP3/Caspase-1/GSDMD pathway and inhibiting pyroptosis. In vivo, RES reduces GSDMD-N levels in rats with SCI, promotes functional recovery, and thus promotes recovery from SCI. Therefore, we concluded that RES increases the level of miR-124-3p, which targets DAPK1, regulates the NLRP3/Caspase-1/GSDMD pathway, inhibits pyroptosis and alleviates SCI.