MiRNA-202-3p Regulates Neuroinflammation In Spinal Cord Injury Through Nf-?B Signaling Pathway By TLR4 And TRAF6 Target Spot

Objective:Investigate the role of miR-202-3p in the inflammatory response after spinal cord injury(SCI).Explore the possible mechanism of miR-202-3p's neuroinflammatory response after SCI.Method:SD rats of suitable age and weight were selected to construct spinal cord injury model,and the histopathological changes of sham operation group and spinal cord injury group were observed.At the same time,the spinal cord injury rats were divided into negative control group,miR-202-3p group and anti-miR-202-3p group.The cells were transfected at the cell level.In vitro models were divided into si-tlr4 transfection group,si-traf6 transfection group,anti-miR-202-3p transfection group and negative transfer group The expression of miRNA and its regulation on inflammatory response after spinal cord injury in rats were observed in the staining group,and the specific mechanism was studied.Result:In our rat model of spinal cord injury,BBB score of spinal cord injury group was significantly inhibited(P<0.01),and he staining showed a lot of hemorrhage and inflammatory cell infiltration in spinal cord tissue.At the same time,the expression of mir-202-3p in group C was detected by RT-qPCR(P<0.01).In vitro cell model,after siRNA transfection of TLR4 and TRAF6,the downstream inflammatory pathway and the expression of inflammatory factors were inhibited(P<0.01).When miR-202-3p was down regulated,TRAF6/TLR4/NF-?B signaling pathway was established and activated,which played a role in promoting inflammatory response in spinal cord injury model.Meanwhile,overexpression of miR-202-3p inhibited the inflammatory response and TLR4/TRAF6/NF-?B signaling pathway in spinal cord injury model.This suggests that TLR4 and TRAF6 attenuate the pro-inflammatory effect of anti-miR-202-3p-mimics on inflammatory response after spinal cord injury through NF-?B signaling pathway.In addition,we also found that the inactivation of TLR4,TRAF6 or NF-?B also reduced the pro-inflammatory effect of anti-miR-202-3p-mimics on inflammatory response in spinal cord injury model.Conclusion:(1)HE staining showed that the water content of spinal cord tissue increased,and a large number of inflammatory cells infiltrated in the site of spinal cord injury,suggesting that inflammation may be an important pathophysiological process after spinal cord injury.(2)After SCI,the content of miR-202-3p decreased significantly,while the expression of downstream inflammatory factors such as TNF-?,IL-6 and IL-18 increased significantly.(3)There was a negative correlation between miR-202-3p and its target genes TRAF6 and TLR4 after SCI.(4)miR-202-3p down regulates NF-?B signaling pathway targeting TLR4 and TRAF6.Meanwhile,it can promote neuroinflammatory response in spinal cord injury.