Mdivi-1 通过抑制少突胶质细胞凋亡信号通路发挥髓鞘保护作用

AIM：To investigate the therapeutic effect of mitochondrial fission inhibitor-1（Mdivi-1）on experi⁃ mental autoimmune encephalomyelitis（EAE）in mice，and to explore its mechanism. METHODS：The mice immunized with myelin oligodendrocyte glycoprotein peptide fragment 35-55（MOG_35-55）were randomly divided into DMSO model group and Mdivi-1 intervention group. All mice were sacrificed on the 28th day after the first immunization. The demyelination was analyzed by Luxol fast blue staining. The protective mechanism of Mdivi-1 in the spinal cord tissue was investigated by immunofluorescence staining，TUNEL staining and the in vitro experiment with MO3. 13 oligodendrocytes treated with staurosporine. The mitochondrial depolarization was detected by JC-1 staining，the cell injury was checked by LDH leakage，and the viability of MO3. 13 oligodendrocytes was determined by MTT assay. RESULTS：Compared with DMSO model group，the demyelinating injury was alleviated and the proportion of apoptotic CC1⁺ oligodendrocytes in Mdivi-1 group was decreased. The cleaved caspase-3，caspase-9，cytochrome C and Bax protein expression levels in the spinal cord of Mdivi-1-treated mice was also attenuated. The in vitro MO3. 13 cell experiments suggested that Mdivi-1 inhibited MO3. 13 cell mitochondrial depolarization，attenuated the cell damage and increased the cell viability. CONCLUSION：Mdivi-1 pro⁃ tects against the myelin injury in EAE mice，which may be related to the suppression of oligodendrocyte apoptosis.