An Experimental Study Of The Effects Of PPAR-γ Agonists On Acute Experimental Autoimmune Encephalomyelitis, In Rats

Objective: This study's objectives were to ⑴ investigate theefficacy of PPAR-γ agonist Rosiglitazone and non-steroidalantiinflammatory drugs (NSAIDs) Ibuprofen and their mode of action inexperimental autoimmune Encephalomyelitis (EAE) , which is a model tosimulate inflammatory aspects of Multiple sclerosis. ⑵ characterize theclinical features, the incidence of this disease in Wistar rats with EAE toevaluate dependability of the animal model. ⑶ determine the level of theexpression of TNF-α mRNA and Calpain further to evaluate efficacy andmechanism of the two agents and provide some experimental evidences forclinical therapies in MS. Methods: All of the experimental Wistar rats were inoculatedintradermal injection with the emulsion homogenate contained spinal cordof guinea pig and complete Freund's adjuvant in feet. The experimental ratswere assigned to four groups randomly,the normal control group, the EAEmodel group, Rosiglitazone treated group and Ibuprofen treated group.There are 8 rats in each group. Respectively, Rats were given the twoagents by oral gavage from the first day to 18th day after initialimmunization. The dosage of rosiglitazone was 4mg·kg-1·d-1, Ibuprofen 100mg·kg-1·d-1. The rats in normal control group were treated in stead of equalnormal saline (N.S). We have investigated the clinical signs and scores ofthe animals on the scale of koh's standard. 18th day after initialimmunization, All rats were killed and detected the expression of TNF-αmRNA and Calpain by the RT-PCR and Western Blot. Results: The animal model we induced showed typical clinicalcharacters and the pathological changes EAE. The expression of TNF-αmRNA was significantly increased in EAE group compare with normalcontrol group (P<0.01). The expression of TNF-α mRNA were significantlydecreased in Rosiglitazone treated group and Ibuprofen treated groupcompare with EAE group (P<0.01). The transcriptional expression ofm-Calpain as examined by RT-PCR was not significantly increased in EAEgroup(P > 0.05). However, the expression of Calpain protein wassignificantly increased in EAE rats compare with normal control group(P<0.01). The efficacy between rosiglitazone and Ibuprofen was nosignificant different. Conclusions: 1)The method of establishing the model of EAE wasstable and reliable in our study. 2)PPAR-γ agonists rosiglitazone andnon-steroidal antiinflammatory drugs (NSAIDs) Ibuprofen can improve theclinical symptoms and signs of EAE in rats, and down modulate the levelof the expression of TNF-αmRNA and Calpain protein. These resultssuggested that orally administered PPAR-γ agonists rosiglitazone andIbuprofen could provide therapeutic benefit in EAE or MS. 3)Our findingssuggested that Calpain played a major role in demyelination in EAE. Thelevel of the expression of Calpain protein indicates the efficacy of thetherapeutic drugs.