The Effect And Mechanism Of NMDAR And Memantine Hydrochloride In Intervertebral Disc Degeneration

Objective: To investigate the effect and mechanism of NMDAR and its antagonist memantine hydrochloride in intervertebral disc degeneration.Methods:(1)Human normal and degenerated nucleus pulposus tissues were collected,and Western blot was used to detect the expression of degeneration-related indexes and NMDAR1;a mouse intervertebral disc degeneration model was constructed,and the structure of the intervertebral disc was observed by Safranin O-Fast Green Staining,and NMDAR1 was detected by immunofluorescence.(2)q RT-PCR,Western blot and ELISA were used to detect the expression of NMDAR1,p-NMDAR1 and matrix degradation indicators in mouse degenerated nucleus pulposus cells under the intervention of memantine hydrochloride;(3)Western blot,ROS test and NO test were used to detect The expression of inflammatory indexes,apoptosis indexes and oxidative stress indexes of degenerated nucleus pulposus cells in mice under the intervention of memantine hydrochloride,and the cell death was detected by live dead cell staining;(4)Safranin O-Fast Green Staining and histological scoring were used to evaluate the degree of intervertebral disc degeneration in mice lumbar spine instability model under the intervention of memantine hydrochloride,and immunohistochemistry was used to detect the expression of NMDAR1 and matrix degradation indicators.Results: NMDAR1 expression was found in human nucleus pulposus tissue,mouse nucleus pulposus tissue and annulus fibrosus,and the expression of NMDAR1 increased in degenerated intervertebral discs;(2)Memantine hydrochloride could inhibit the expression and activation of NMDAR1,reduce the degradation of nuclear cell matrix and enhance collagen synthesis;(3)Memantine hydrochloride can reduce the inflammatory response of mouse nucleus pulposus cells,relieve cell apoptosis,oxidative stress,and reduce the death of nucleus pulposus cells;(4)Memantine hydrochloride can inhibit the expression of NMDAR1 in the intervertebral disc of mice and relieve the degeneration of the intervertebral disc.Conclusions: The expression of NMDAR1 is increased in human and mouse degenerative intervertebral discs.Memantine hydrochloride can inhibit the matrix degradation,inflammatory response,apoptosis and oxidative stress of degenerative nucleus pulposus cells,and relieve intervertebral disc degeneration.The effect may be through the inhibition of NMDAR1 expression and activation.