Dexmedetomidine suppresses oxidative stress and inflammation of nucleus pulposus cells by activating the PI3K/Akt signaling pathway.

Abstract

Objective: Intervertebral disc degeneration (IVDD) is very common in the elderly, so it is particularly important to find appropriate prevention or treatment. The aim of this study was to explore the effect of dexmedetomidine (DEX) on the degeneration of nucleus pulposus (NP) cells and its mechanism. Methods: We established a mouse model of IVDD and cultured mouse NP cells and treated them with IL-1β and DEX. The effect of DEX on NP cells was determined by detecting the extracellular matrix of NP cells, changes in ROS levels and inflammatory mediators. LY294002, a PI3K inhibitor, is used to inhibit the activity of the PI3K/Akt signaling pathway. The effect of DEX on the PI3K/Akt signaling pathway was determined by studying the effects of DEX on PI3K/ Akt signaling pathway-related molecules and the effect of LY294002 on NP cells degeneration. DEX significantly increased the disc height index and attenuated IVDD in mice. Results: DEX significantly inhibited the expression of MMP3/9 in NP cells, effectively inhibiting the degradation of extracellular matrix. In addition, oxidative stress levels and inflammatory levels in NP cells are also attenuated by DEX. The expression of PI3K, Akt and p-Akt was significantly increased in DEX-stimulated NP cells, indicating that DEX increased the activity of the PI3K/Akt signaling pathway. DEX promotes PI3K/Akt signaling pathway, inhibits oxidative stress and inflammatory of NP cells, thereby slowing the degeneration of NP cells. Conclusion: DEX promotes PI3K/Akt signaling pathway, inhibits oxidative stress and inflammatory of NP cells, thereby slowing the degeneration of NP cells.