Amelioration Of Experimental Autoimmune Encephalomyelitis Brain And Expression Of IL-17,TGF-β1 In Rats By Atorvastatin

Objective:This study was design to explore the effects of atrorvastatin, a synthetic inhibitor of HMG-CoA reductase,on induced experimental autoimmune encephalomyelitis(EAE) in Wistar rats,and discuss the underlying immuno-regulatory mechanism for EAE through the orientation of interleukin-17(IL-17) and transforming growth factor-β1(TGF-β1).Methods:The animal model was established in female Wistar rats by immunizing rats with guinea pig spinal cord homogenate(GPSCH), complete freund's adguvant(CFA) and pertussis vaccine (PV).Seventy wistar rats were randomly divided into seven groups:ten rats in normal group,ten rats in normal control group,ten rats in EAE group,different doses atrorvastatin group and Prednisone group,Rats were fed with atrorvastatin in different doses atrorvastatin group,while prednisone group were fed with prednisone,starting from the immunization to the day rats were sacrificed. All the animals were sacrificed at the 16th 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 with the aid of hematoxylin-eosin and Luxol Fast Blue myelin staining. The number of inflammation focus in the central nervous system (CNS) was counted under the optical microscope.The expressions of IL-17 and TGF-β1 in brain tissue were detected by using immunohistochemistry technique.Experimental results were analyzed with SPSS 17.0.Results:1.No rats in normal and normal control group have disease.Comparing to EAE group,the EAE of small dose Atrorvastatin group's rats have degraded weight loss and neurological deficit scores(p<0.05)while have no different in morbility and eclipse period. Other doses Atrorvastatin groups and Prednisone group have prolonged eclipse period,degraded morbility, weight loss and neurological deficit scores(p<0.05).2.The CNS tissue's hematoxylin-eosin(HE)staining histopathology results of EAE group's rats indicate that CNS already have inflammation while no change in normal and normal control group.Comparing to EAE group,the extent and amount of the inflammation focus decreased in the different doses Atrorvastatin and Prednisone group(p<0.05).Comparing to the Prednisone group,the general and the high doses Atrorvastatin groups' CNS inflammation focus have no difference(p>0.05).Luxol fast bule-Cresyl fast violet myelin staining indicated no demyelination in normal and normal control group.In EAE group the demyelination lesions were the most serious. Dispersive demyelination focuses could be seen casually in different doses Atrorvastatin groups and Prednisone group.3.Immunohistochemistry and image analysis results of each group rats indicate that the CNS expression level of IL-17 and TGF-β1 has increase in the EAE group comparing with normal and normalcontrol group(p<0.05). Comparing to the EAE group,different doses Atrorvastatin and Prednisone group's rats have lower level of IL-17 and higher level of TGF-β1(p<0.05). Comparing to the high dose Atrorvastatin group,Prednisone group's level of IL-17 and TGF-β1have no difference(p>0.05).Conclusion:1.Atrorvastatin has amelioration effect on EAE rats and the effects were in dose-dependent fashion.2.One of the mechanisms related to atrorvastatin's amelioration effect on EAE is down-regulation the level of IL-17 and up-regulation the level TGF-β1 in the CNS.