| ObjectiveIn our study, we administrate different dose simvastatin to the rats of experimental autoimmune encephalomyelitis (EAE)-an animal model of MS, in order to investigate the therapeutic potential and mechanism in treatment of EAE and the expression of IL-10 in the central nervous system(CNS).MethodsThe animal model was established in female Wistar rats by immunizing rats with guinea pig spinal cord homogenate (GP-SCH), complete freund's adguvant (CFA) and pertussis vaccine (PV). Sixty wistar rats were randomly divided into four groups: each fifteen rats in normal control group, EAE group, low dose simvastatin treatment group and high dose simvastatin group, then the four group were randomly divided into three subgroups,each subgroup have five rats. Rats were fed with simvastatin (2 mg/kg·d) in low dose simvastatin group, while high dose simvastatin group were fed with simvastatin (10 mg/kg·d), starting from the 1st day after immunization to the day rats were sacrificed. The animals of the three subgroups of four groups were sacrificed at the 11th day, the 15th day and the 21th day. The severity of EAE was scored on a scale 0-5 according to the signs and symptoms. Histological examinations were performed on the sections of brain and spinal cord with the aid of hematoxylin-eosin staining. The number of inflammation in the central nervous system (CNS) was counted under the optical microscope. And the expressions of IL-10 in brain tissue were detected by using immunohistochemistry technique and optical density detection. Experimental results were analyzed with SPSS13.0.Results1. No rats in normal control group have disease. Comparing to EAE group and the low dose simvastatin group, the EAE of high dose simvastatin group's rats have prolonged eclipse period(p<0.05), degraded morbility, weight loss and neurological deficit scores(p<0.05). Comparing to EAE group, the EAE of low dose simvastatin group's eclipse period, morbility, weight loss and neurological deficit scores have no significant difference(p>0.05).2. The CNS tissue's hematoxylin-eosin(H-E) staining histopathology results of EAE group's rats indicate that CNS already have inflammation focus at the 11th day, the extent and amount of the inflammation focus increased at the 15th day, then decreased at the 21th day. Comparing to the three subgroups of EAE group and low dose group, the same subgroup of high dose group have decreased CNS inflammation focus(p<0.05). Comparing to the three subgroups of EAE group, the same subgroup of low dose's CNS inflammation focus have no significant difference(p>0.05).3. Immunohistochemistry and image analysis results of each group rats indicate that the CNS expression level of IL-10 has no significant difference in the 11th day subgroup(p>0.05)of the EAE group and the low dose group, up-regulated in the other subgroup(p<0.05)comparing with normal control group. With the prolonged course of disease, the 15th day subgroup comparing with the 11th day , the 21th day subgroup comparing with the 15th day have higher level of IL-10 in the CNS(p<0.05). Comparing to the same subgroup of the EAE group and low dose group, high dose group's rats have higher level of IL-10 in the CNS(p<0.05). Comparing to the subgroup of EAE group, the same subgroup of low dose's CNS level of IL-10 have no significant difference(p>0.05).Conclusion1. High dose Simvastatin have amelioration effect on EAE rats.2. One of the mechanisms related to Simvastatin's amelioration on EAE is probably up-regulation of the level of IL-10 in the CNS. |
