| Objective: To investigate the intervention effect of Tripterygium wilfordii ployglycosidium (TWP) on induced experimental autoinnune encephalomyelitis (EAE) in Wistar rats, compare the therapeutic effect of TWP with prednisone (PRD) using two different doses, and explore the underlying immunoregulatory mechanism of EAE.Methods: The animal model was established in Wistar rats by immunizing rats with guinea pig spinal cord homogenate (GP-SCH), complete freund's adguvant (CFA) and pertussis vaccine (PV). Sixty-five wistar rats were randomly divided into five groups: control group, EAE group, TWP group I, TWP group II and PRD group. Rats were fed with TWP (10mg/kg.d) in TWP group I, TWP (30mg/kg.d) in group II , while PRD group were fed with prednisone (5mg/kg.d), starting from the 1st day after immunization to the day rats were sacrificed. The animals of control group were sacrificed at the 15th day. The animals of other groups were divided into three subgroups: the 11th day sacrificed, the 15th sacrificed and the 21st sacrificed. 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 and luxol fast blue's (LFB's) myelin staining. The number of inflammation in the central nervous system (CNS) was counted under the optical microscope. And the expressions of NF-κB p65 and TNF-αin brain tissue were detected by using immunohistochemistry technique. Experimental results were analyzed with Spss 13.0.Results:1. The morbility of control group is 0%. The morbility of EAE group is 93.3%. The clinical symptoms of EAE occurred about 11 days after immunization were induced, which lasted 10～12 days. The peak of clinical symptoms took place at the 15th day, meanwhile the histopathology change in the CNS is also most distinct: perivascular cuffing with mononuclear cells, partly neuronal degeneration and demyelination. The intervention groups had lower morbility (TWP group I 73.3%, TWP group II 53.5 %, PRD group 46.7%) with 1～2 days delay of onset, and lighter clinical symptoms. The number of inflammation in the CNS was decreased significantly (intervention groups vs EAE group, P<0.05; TWP group II, PRD group vs TWP group I , P<0.05).2.EAE group: Comparing to control group, the expressions of NF-κB p65 and TNF-αin brain tissue of EAE were increased significantly at the 11th day (P<0.05). Comparing to the 11th day, the expressions of NF-κB p65 and TNF-αin brain tissue were increased significantly at the 15th day (P<0.05). Comparing to the 15th day, the expressions of NF-κB p65 and TNF-αin brain tissue were increased significantly at the 21st day (P<0.05).3. TWP group I , TWP group II and PRD group: Comparing to control group, the expressions of NF-κB p65 and TNF-αin brain tissue of intervention groups were increased significantly at the 11th day (P<0.05). Comparing to the 11th day, the expressions of NF-κB p65 and TNF-αin brain tissue were increased significantly at the 15th day (P<0.05). Comparing to the 15th day, the expressions of NF-κB p65 and TNF-αin brain tissue were increased significantly at the 21st day (P<0.05). Comparing to EAE group, the expressions of NF-κB p65 and TNF-αin brain tissue of intervention groups were decreased significantly at the same time (P<0.05). Comparing to TWP group I, the expressions of NF-κB p65 and TNF-αin brain tissue of TWP group II and PRD group were decreased more significantly at the same time (P<0.05). There were no difference of the expressions of NF-κB p65 and TNF-αin brain tissue between TWP group II and PRD group at the same time (P>0.05).Conclusion:1. NF-κB p65 and TNF-αmight play roles in EAE.2. TWP could effectively moderate EAE in rats, to some extent the effect was dose-dependent, which might be mechanistically related to down- regulation of NF-κB p65 and TNF-α.
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