Mechanism Of The Influence On Intervertebral Disc Degeneration By Inhibiting Oxidative Stress And The NF-kappa B Pathway In Bmi-1 Null Mice

[Objective]The purpose of this study is to investigate the role of Oxidative Stress and the NF-kappa B pathway in alleviating the intervetebral disc degeneration induced by bmi-1-knockout.[Methods]We design 4 groups for our study,8 WT mice or bmi-1-/-mice are in each group.Mice in group A are WT mice feed with normal food,bmi-1-/-mice feed with normal food in group B,bmi-1-/-mice feed with NAC in group C.bmi-1-/-mice treatment with intraperitoneal injection with IDM-0354 in group D.Samples of group A,B and C were obtained after one month,while samples of group D after one week.We observed the morphological changes of disc in mice by Hematoxylin-Eosin staining and Saffron staining.Proteins and RNA were extraction to evaluate the indicators of Oxidative Stress,NF-?B and catabolism.[Results]Histological staining showed that morphology of NP changes in bmi-1-/-mice,the arrangement of AF surrounding is more disordered than the wild-type mice,the expression of ECM(proteoglycan)was higher than that of wild type mice.Morphological changes have improved in bmi-1-/-mice after treatment with NAC or IMD.Results of protein imprinting technology show that the level of oxidative stress,as well as the expression of matrix degrading enzymes in the intervertebral disc of bmi-1-/-mice,was higher than that in wild type mice.The level of oxidative stress and the expression of matrix degrading enzymes decreased significantly in bmi-1-/-mice after treatment with NAC or IMD.[Conclusion]Deletion of Bmi-1 gene is an important factor to accelerate the degeneration of intervertebral disc.Inhibition of oxidative stress or NF-kappa B signaling pathway can correct Bmi-1-deficiency-induced disc degeneration.This study provides a new target for delaying or treating the occurrence and development of disc degeneration.