关键词: 脑脊髓炎, 自身免疫性, 实验性；Toll样受体4；NF-κB；炎症；白细胞介素类；肿瘤坏死因子α；依达拉奉右莰醇；TLR4/NF-κB信号通路

Abstract: Objective　To investigate the effect and mechanism of edaravone dexborneol on the inflammatory response in mice with experimental autoimmune encephalomyelitis (EAE). Methods　Thirty female C57BL/6 mice were randomly divided into the blank group, the model group and the edaravone dexborneol intervention group, with 10 mice in each group. Except for the blank group, EAE model was induced by myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) polypeptide in the other two groups. From the day after modeling, mice in the edaravone dexborneol intervention group were intraperitoneally injected with edaravone dexborneol 12.5 mg/kg, while the mice in the blank group and the model group were intraperitoneally injected with the equal amount normal saline, once a day for consecutive 14 days. The behavioral changes of mice were observed, and neurological dysfunction scores were performed. HE and LFB staining were used to detect spinal cord pathological changes. The mRNA expression levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in brain homogenate were detected by real-time fluorescence quantitative PCR. The protein expression levels of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) in spinal cord tissue were detected by Western blot assay. Results　None of the mice in the blank group had the disease, and the other two groups of mice had different degrees of disease. Compared with the model group, the incubation period and peak period were delayed in the edaravone dexborneol intervention group, and neurological deficit scores in peak period decreased (P＜0.01). No abnormality was found in spinal cord tissue structure in mice of the blank group, and a large number of inflammatory cell infiltration, myelin structure disorder were found in the spinal cord tissue of the model group. Compared with the model group, inflammatory cell infiltration was reduced and myelin structure disorder was improved in the edaravone dexborneol intervention group. Compared with the blank group, the IL-1β, IL-6, TNF-α mRNA expression levels in brain tissue homogenate and the TLR4, NF-κB p65 protein expression levels in spinal cord tissue were significantly increased in the other two groups (P＜0.05). After intervention with edaravone dexborneol, the above changes induced by modeling were reversed (P＜0.05). Conclusion　Edaravone dexborneol can effectively reduce the inflammatory response in EAE mice, and its mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway activation.

Key words: encephalomyelitis, autoimmune, experimental, Toll-like receptor 4, NF-kappa B, inflammation, interleukins, tumor necrosis factor-alpha, edaravone dexborneol, TLR4/NF-κB signaling pathway