Changes of Keap1/nuclear factor erythroid 2-related factor 2 signaling pathway in mice with spinal injury and intervention effect
Objective To investigate the changes of Keap1/nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway in rats with spinal injury and the effect of glycyrrhiza chalcone on the treatment of spinal injury rats.Methods Totally,30 SD mice were randomly divided into sham operation group,spinal injury group and intervention group.Mice in sham operation group received spinal injury free opera-tion,and mice in spinal injury group and intervention group received contusion method to establish spinal injury model.Mice in the intervention group were treated with 60 mg/kg glycyrrhizin via the tail vein.Mice in sham operation group and spinal injury group were injected with equal volume of normal saline through the tail vein.After 2 weeks of treatment,the neurological function of the three groups was analyzed by bas-so mouse scale(BMS)score,and the motor function of the mice was scored by Basso,Beattie and Bresna-han score(BBB).Enzyme-linked immunosorbent assay(ELISA)was used to analyze the serum tumor nec-rosis factor-α(TNF-α),transforming growth factor-[3(TGF-β)and interleukin-1β(IL-1β)levels.The contents of superoxide dismutase(SOD)and malondialdehyde(MDA)were determined by thiobarbituric acid method and xanthine oxidase method.The number of neurons was calculated by Nissl staining.The apoptosis level of mouse spinal cord cells was analyzed by Western blotting.One-way analysis of variance was used to compare the measurement data between groups.Results The BBB score and BMS score in the intervention group[(12.50±2.92),(5.80±1.14)points]were significantly higher than those in the spi-nal injury group[(5.30±1.64),(3.20±1.23)points,t=6.810,4.914,P＜0.05].The level of MDA in the intervention group[(8.09±0.61)nmol/ml]was significantly lower than that in the spinal injury group[(12.78±1.94)nmol/ml,t=7.296,P＜0.05].SOD activity in the intervention group[(139.85±9.41)nU/ml]was significantly higher than that in the spinal injury group[(101.28±7.30)nU/ml,t=5.238,P＜0.05].The levels of serum inflammatory factors TNF-α,IL-1β and TGF-βin the intervention group[(110.38±9.02),(58.88±8.01),(40.76±2.77)nmol/ml]was significantly lower than that in the spinal injury group[(174.40±12.62),(93.33±3.85),(56.39±2.52)nmol/ml,t=13.050,12.260,13.200,P＜0.05].The number of Pap bodies in the intervention group(31.40±4.19)was significantly greater than that in the spinal injury group(20.30±2.91,t=6.887,P＜0.05).The protein expression levels of Nrf2 in the intervention group(0.74±0.06)were sig-nificantly higher than those in the spinal injury group(0.51±0.10,t=6.320,P＜0.05).The expression levels of cysteine-aspartic acid protease-3(Caspase-3)and B cell lymphoma/leukemia-2 associated X pro-tein(bax)protein in the intervention group(0.66±0.06,0.86±0.08)were significantly lower than those in the spinal injury group(0.91±0.06,1.43±0.08,t=9.504,15.890,P＜0.05).Conclusion Keap1/Nrf2 signaling is involved in the progression of spinal cord injury in mice.Glycyrrhiza chalcone can significantly activate Keap1/Nrf2 pathway,reduce spinal cord inflammation and oxidative stress,and improve nerve function.
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