Amelioration Of Experimental Autoimmune Encephalomyelitis And Expression Of LINGO-1 In The Brain Of Rats By Atorvastatin

ObjectiveTo obverse the effect of atorvastatin on the incidence of experimental autoimmune encephalomyelitis (EAE) in rats, neural function score, histopathological changes and periventricular LINGO-1 expression, and to investigate the amelioration of atorvastatin on the EAE model and its possible mechanism.MethodThe animal model was established in female Wistar rats by immunizing them with guinea pig spinal cord homogenate (GP-SCH), complete freund's adguvant (CFA) and pertussis vaccine (PV). Seventy-eight wistar rats were randomly divided into five groups:six rats in normal control group, the rest rats were equally divided into the EAE group, low-dose atorvastatin group (2mg/kg-d), high-dose atorvastatin group (8mg/kg-d) and prednisone group (5mg/kg-d).Corresponding drugs were given once a day, until the day before when they dead. Normal control group were sacrificed at 15th day, and the other three groups were randomly divided into three sub-groups, each sub-group had six rats, and were sacrificed on different times at the 11th day, the 15th day and the 21th day. The severity-eight of EAE was scored on a scale 0-5 according to signs and symptoms.Histological examinations were performed on the sections of brain with the aid of hematoxylin-eosin staining. The number of inflammation in the central nervous system (CNS)was counted through the optical microscope.And the expressions of LINGO-1 in brain tissue were detected by using immunohistochemistry technique and optical density detection.Experimental results were analyzed with SPSS 17.0.Result1.The clinical performance:The rats in normal control group were without EAE, and the neural function score was 0.Comparing with the EAE group, the EAE of high-dose atorvastatin group and prednisone group's rats have prolonged eclipse period (p<0.05),degraded morbility and neural function score (p<0.05);but the EAE of low-dose atorvastatin group's rats had no significant difference (p>0.05).There was no significant difference between the high-dose atorvastatin group and the prednisone group (p>0.05).2.The results of the hematoxylin-eosin(H-E) staining histopathology in EAE group indicated that CNS already had had inflammation focuses on the 11th day, the extent and amount of the inflammation focuses increased on the 15th day, then decreased on the 21th day. Comparing with the extent and amount of the inflammation focuses of the same period subgroup of EAE group, the same period subgroup of high-dose atorvastatin group and prednisone group had decreased (p<0.05),but the low-dose atorvastatin group had no significant difference (p>0.05).There were no significant differences between the same period subgroups of high-dose atorvastatin group (p>0.05). 3.The results of immunohistochemistry and image analysis in EAE groups indicated that the expression level of LINGO-1 were down-regulated on the 11th and the 15th day (p<0.05),but up-regulated on the 21th day (p<0.05)comparing with normal control group.Comparing with the same period subgroup of EAE group, the low-dose atorvastatin group had no significant difference (p>0.05);on the 11th day, the same period subgroups of high-dose atorvastatin group and prednisone group had no significant difference (p>0.05);on the 15th and the 21th day, the same period subgroups of high-dose atorvastatin group and prednisone group were up-regulated (p<0.05),but the high-dose atorvastat group was more significant (p<0.01) on the 21th day.Conclusion1.Atorvastatin may have protective effect on EAE rats,which is positively related with the dose to some extent.2.Atorvastatin influences the level of LINGO-1 in CNS.This may be one of the protective mechanisms in EAE.