الملخص
OBJECTIVE To investigate whether matrine exerts improvement effect on experimental autoimmune encephalomyelitis (EAE) mice by regulating ferroptosis pathway. METHODS Totally 30 female C57BL/6 mice were randomly assigned into normal group, model group and matrine group, with 10 mice in each group. Model group and matrine group were given antigen emulsion containing inactivated Mycobacterium tuberculosis and MOG35-55 to induce EAE model. Matrine group was injected with Matrine injection (50 mg/kg) intraperitoneally since the 7th day after immunization; normal group and model group were given constant volume of normal saline intraperitoneally, once a day, since 18th day after immunization. The neurofunctional score of mice was recorded, and hematoxylin and eosin staining and Luxol fast blue staining were used to observe inflammatory cell infiltration and demyelination in spinal cord tissue. The quantitative reverse transcription PCR and Western blot assay were performed to determine the mRNA expressions of transferrin receptor 1 (TFR1), nuclear receptor coactivator 4 (NCOA4) and hephaestin (Heph), and the protein expressions of system Xc- (xCT) and glutathione peroxidase 4 (GPx4). RESULTS Compared with normal group, accumulative neurofunctional score was significantly increased in model group (P<0.01); inflammatory cell infiltration and demyelination were obvious in spinal cord tissue, and related scores were increased significantly (P<0.01). The mRNA expressions of TFR1 and NCOA4 in myelin tissue were up-regulated significantly, while the mRNA expression of Heph and the protein expressions of xCT and GPx4 were down-regulated significantly (P<0.05 or P<0.01). Compared with model group, above indexes of matrine group were all improved significantly (P<0.05 or P<0.01). CONCLUSIONS Matrine can improve EAE mice, the mechanism of which may be associated with regulating iron metabolism pathway and xCT/GPx4 pathway in ferroptosis.