Mechanisms of inhibition of nucleus pulposus cells pyroptosis through SDF1/CXCR4-NFkB-NLRP3 axis in the treatment of intervertebral disc degeneration by Duhuo Jisheng Decoction

Abstract

Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain and the most common health problem in the world. Inflammasomes, which is mainly caused by NLRP3, mediated nucleus pulposus pyroptosis has been discovered to be strongly related to IVDD. In addition, Duhuo Jisheng Decoction (DHJSD) has anti-inflammatory and regulatory effects on NLRP3 inflammasome, but the molecular mechanism of whether DHJSD can regulate pyroptosis through NLRP3 to treat IVDD is unclear. In this study, we used a bioinformatics way to discover the molecular mechanism of DHJSD regulation of pyroptosis in IVDD, and validated our predictions through vitro and vivo experiments. Through bioinformatics, we found that NLRP3, GSDMD, IL-1βand other hub proteins of pyroptosis were highly expressed in IVDD SD rats, and network pharmacology discovered that DHJSD may control cellular senescence, apoptosis, and pyroptosis in order to treat IVDD. Additional findings demonstrated that DHJSD could successfully treat IVDD brought on by imaging and histomorphological analysis. Western blot showed that NLRP3, a key protein of pyroptosis, was elevated in rat degenerated nucleus pulposus tissue and lipopolysaccharide-treated Nucleus pulposus Cells (NPCs), and that DHJSD intervention was effective in reducing LPS-induced inflammatory responses and further suppressing the expression of pyroptosis related proteins to improve IVDD. The specific mechanism is that DHJSD inhibits NPCs pyroptosis via the SDF-1/CXCR4-NF-kB-NLRP3 axis. In conclusion, we revealed the intrinsic mechanism of DHJSD regulation of NPCs pyroptosis to improve IVDD and its intrinsic value for IVDD treatment.