The Effects Of Ruscogenin Intervention On Inhibiting Inflammation In A Mouse Model Of Spinal Cord Injury

Objective:To explore the effect of Ruscogenin(Rus)on the recovery of neurological function after spinal cord injury(SCI)in mice.To explore the role and effects of Rus in the inflammatory response after SCI,and to analyze the inflammatory processes involved in Rus after SCI at the in vivo and in vitro levels,in order to find potential pathways for the clinical treatment of SCI.Methods:In vivo model of SCI was successfully created,and the recovery of motor level was assessed by comparing the motor score of BMS,Rivlin slant plate test and Catwalk gait analysis in different groups of Rus intervention,and the expression level of inflammatory factors associated with SCI in each group was compared by Western Blot assay.Microglia inflammation model was constructed by BV-2 cells in vitro,and the cytotoxicity results were compared by CCK-8 assay under Rus intervention in different BV-2 cell groups;the expression levels of relevant inflammatory factors and NF-κB pathway-related factors were compared by Western Blot assay in each BV-2 cell group inflammation model.Results:The RUS(5mg/kg/d)group showed motor improvements in BMS motor scores,Rivlin’s inclined plate test and Catwalk gait analysis results compared to the other groups of mice.The Rus(1mg/kg/d),Rus(5mg/kg/d)and Rus(10mg/kg/d)groups were lower than the SCI group in terms of inflammation levels,with Rus(5mg/kg/d)being the most pronounced.The CCK-8 assay showed a significant toxic effect on BV-2 cells at Rus≥100μmol/L,which determined the subsequent experimental groupings.Western Blot experiments on different BV-2 cell groups showed that Rus(1μmol/L),Rus(5μmol/L),Rus(10μmol/L)and Rus(50μmol/L)groups were lower than the LPS group in terms of inflammation levels,and Rus(5μmol/L)was the most pronounced.Compared with the LPS group,NF-κB and IκB-α expression was up-regulated and p-NF-κB and p-IκB-αexpression was down-regulated in the LPS+BAY 11-7082 group compared with the LPS(5μmol/L)group,with the same trend of action in the LPS+BAY 11-7082 group and the LPS+Rus(5μmol/L)group.Conclusion:Rus can promote motor function recovery and improve limb coordination in mice after SCI.Rus attenuated the expression of inflammatory factors such as IL-1β,IL-6 and TNF-α in the percussion segment of the mouse SCI model.Rus has the potential effect of reducing the expression of inflammatory factors in BV-2 cells after LPS treatment and inhibiting the inflammatory response in the BV-2 cell inflammation model.BAY 11-7082 with Rus at certain doses inhibits the activation effect of LPS in the BV-2 inflammation model NF-κB pathway.