Objective To observe the therapeutic effect and mechanism of Aucubin on rats with intervertebral disc degeneration(IDD).Methods Forty rats were randomly divided into five groups,i.e.,sham-operated group,model group,Aucubin group,Aucubin+Resveratrol[nuclear factor-kappa B(NF-κB)pathway activator]group,and Aucubin+ML385(Nrf2 inhibitor)group,with eight rats in each group.Except for the sham-operated group,rats in all groups were prepared for the IDD model using the annulus fibrosus puncture method.After successful modeling,each group was given corresponding intervention.After the end of intervention,the expression of matrix metalloproteinase(MMP)-3 and collagen type Ⅱ(COLⅡ)in the nucleus pulposus of intervertebral discs was detected by immunohistochemical analysis.Terminal deoxynucleotidyl transferase dUTP nick labeling(TUNEL)was used to determine the apoptosis of nucleus pulposus cells in the intervertebral discs.And malondialdehyde(MDA)and superoxide dismutase(SOD),interleukin(IL)-1β,IL-6,and tumor necrosis factor α(TNF-α)levels in the nucleus pulposus of intervertebral discs were detected by colorimetry.Western Blot was used to determine the protein expression levels of MMP-3,MMP-13,COLⅡ,Aggrecan,Bcl-2,caspase-3,p-p65,p65,phosphorylated IκBα(p-IκBα),IκBα,Nrf2,heme oxygenase 1(HO-1),and NAD(P)H:nadph quinine oxidoreductase-1(NQO-1).Results Compared with the sham-operated group,the proportion of MMP-3-positively stained cells was increased in rats in the model group,COLⅡ-positively stained cells was decreased,the apoptosis rate of nucleus pulposus cells was increased,MDA level was increased,SOD level was decreased,the levels of IL-1β,IL-6 and TNF-α were elevated,and the protein expression levels of MMP-3,MMP-13,caspase-3,p-p65/p65,p-IκBα/IκBα and nuclear p65 were decreased,protein expression levels of COLⅡ,Aggrecan,Bcl-2,nuclear Nrf2,HO-1,NQO-1 were increased in the nucleus pulposus of intervertebral discs,the differences being significantly statistical(P＜0.05).Compared with the model group,the proportion of MMP-3-positively stained cells was decreased in rats in the Aucubin group,COLⅡ-positively stained cells was increased,the apoptosis rate of nucleus pulposus cells was reduced,MDA level was decreased,SOD level was increased,the levels of IL-1β,IL-6 and TNF-α were elevated,and the protein expression levels of MMP-3,MMP-13,caspase-3,p-p65/p65,p-IκBα/IκBα and nuclear p65 were increased,protein expression levels of COLⅡ,Aggrecan,Bcl-2,nuclear Nrf2,HO-1,NQO-1 were decreased in the nucleus pulposus of intervertebral discs,the differences being significantly statistical(P＜0.05).Resveratrol and ML385 were able to reverse the ameliorative effects of Aucubin on extracellular matrix degradation,nucleus pulposus apoptosis,oxidative stress and inflammatory response of intervertebral disc tissues in IDD rats to a certain extent.Conclusion Aucubin can reduce nucleus pulposus apoptosis and extracellular matrix degradation in the intervertebral discs of rats with IDD by inhibiting oxidative stress and inflammatory responses,and the mechanism may be related to the regulation of the Nrf2/NF-κB signaling pathway.
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