动物造模,自身免疫性脑脊髓炎 z-bio 2022-06-16 421

　　Objective To investigate the effect of atorvastatin on myelin repair and RhoA/Rock1 pathway in autoimmune encephalomyelitis (EAE) mice.

　　Methods The EAE mouse model was established by immunization with MOG35-55. The mice were randomly divided into blank group, model group, atorvastatin group, high-fat diet group, and high-fat diet + atorvastatin group, with 6 mice in each group. Tovastatin was administered to each mouse by 0.5 mL of suspension per day for 28 consecutive days. The neurological function scores of the mice in each group were detected by hematoxylin-eosin (HE), fast blue (LFB) staining, transmission electron microscopy and immunohistochemical staining methods to detect the inflammatory reaction, demyelination and myelination of the spinal cord tissue of the mice in each group Sheath regeneration; enzyme-linked immunosorbent assay (ELISA) to detect the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) in serum of mice; Western blot ( Western blot was used to detect the protein expressions of RAS homologous gene family member A (RhoA) and Rho-related protein kinase 1 (Rock1) in brain tissue; real-time quantitative PCR (qRT-PCR) was used to detect chondroitin sulfate proteoglycan (NG2), Myelin basic protein (MBP) and brain tissue RhoA, Rock1 mRNA expression.

　　Results Compared with the blank group, the mice in the model group saw more inflammatory cell infiltration, obvious demyelinating changes, partial myelin disintegration, rupture and loss; serum TNF-α, IL-6, NO The content of RhoA, Rock1 protein and mRNA in brain tissue were significantly increased (P<0.01), and the protein and mRNA expression of NG2 and MBP in spinal cord tissue were significantly decreased (P<0.01). Compared with the model group, the mice in the atorvastatin group saw a very small amount of inflammatory cell infiltration, the degree of demyelination was significantly improved, and the levels of TNF-α, IL-6 and NO in the serum of the mice and the RhoA and Rock1 levels in the brain tissue of the mice were significantly reduced. The expression of protein and mRNA (P<0.05), the protein and mRNA expression of MBP and NG2 were significantly increased (P<0.05); the high-fat diet + atorvastatin group significantly decreased the neurological function score, brain tissue RhoA , Rock1 protein expression, significantly increased NG2 mRNA expression.

　　Conclusion Atorvastatin can improve the infiltration of inflammatory cells and demyelination in EAE mice, and reduce the neurological function score of EAE mice with high-fat diet. The therapeutic effect of EAE mice.