The AMPK and NLRP3 inflammasome signaling pathways are reported to participant in the inflammatory responses following spinal cord injury (SCI). Ulinastatin (ULI) is a urinary trypsin inhibitor with excellent anti-inflammatory effects, but the functions of ULI on SCI are rarely reported. Hence, this study was designed to investigate whether ULI could modulate SCI through regulating the AMPK/NLRP3 signaling pathway. Cell Counting Kit-8 (CCK-8) assays were used to investigate whether ULI had cytotoxic effects on BV-2 cells. Basso-Beattie-Bresnahan (BBB) scale, spinal cord water content detection, hematoxylin-eosin (HE) and Nissl stainings were used to investigate the protective effects of ULI on rat SCI. The expressions of inflammatory cytokines were detected by ELISA and RT-qPCR. The expressions of key proteins of AMPK and NLRP3 inflammasome were analyzed by western blot. The CCK-8 assays indicated that ULI did not significantly influence the viability of BV-2 cells at various concentrations below 10,000 U/ml. It was witnessed that ULI could dramatically inhibit the activation of NLRP3 inflammasome via activating the AMPK signaling pathway, thus relieving inflammatory responses. Besides, the in vivo experiment suggested that treatment with ULI remarkably relieve spinal cord edema, ameliorated spinal cord tissue architecture, and improved neurological function following SCI. The findings indicate that ULI significantly ameliorates neurological function following SCI by regulating the AMPK/NLRP3 inflammasome signaling pathway.
Keywords: AMPK; Inflammation; NLRP3 inflammasome; Spinal cord injury; Ulinastatin.
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.