动物造模,自身免疫性脑脊髓炎 z-bio 2022-12-06 339

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

　　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, high-fat diet+atorvastatin group, with 6 mice in each group. Each mouse was given 0.5 mL of atorvastatin suspension every day for 28 days. Neurological function scores of mice in each group were measured by hematoxylin eosin (HE), solid blue (LFB) staining, transmission electron microscopy and immunohistochemical staining; Detection of Tumor Necrosis Factor in Mouse Serum by ELISA- α (TNF- α)、 The expression of interleukin-6 (IL-6) and nitric oxide (NO); Western blot was used to detect the expression of RhoA, Rho related protein kinase 1 (Rock1) in brain tissues; The expression of chondroitin sulfate proteoglycan (NG2), myelin basic protein (MBP) in spinal cord and RhoA, Rock1 mRNA in brain were detected by real-time quantitative PCR (qRT PCR).

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

　　Conclusion Atorvastatin can improve the degree of inflammatory cell infiltration and demyelination in EAE mice, and reduce the neurological function score of EAE mice fed with high-fat diet. The mechanism of action may be related to the regulation of RhoA/Rock1 pathway to improve demyelination, so as to play a therapeutic role in EAE mice.