| Objective Guillain-Barre Syndrome(GBS) is an autoimmune disease of the peripheral nervous system, characterized by multifocal demyelination and inflammation cells infiltration in peripheral nerves and spinal nerve roots._Experimental allergic neuritis(EAN) is a classical animal model to study pathogenetis of GBS. The activation of peripheral nervous myelin antigen specific CD4~+T cell play key roles in the development of EAN. OX40/OX40L is a new co-stimulatory molecules, it appears to be particularly important for regulating the extent of CD4~+ T cell expansion in the primary T cell respons. Rho/ROK plays an important role in various pathological processes, promoting the migration of T cells, inducing the secretion of inflammatory factors, and triggering cell apoptosis and synapse disintegration. Rho-kinase inhibitors may ameliorate the symptoms in many inflammatory diseases. In this study, through observing the expression of mRNA of OX40 and OX40L in the sciatic nerve, spleen, Peripheral blood mononuclear cells and lymph nodes of EAN and the changes of OX40 and OX40L under the influence of Rho-kinase inhibitor, we explored the roles of OX40/OX40L in EAN/GBS process and the molecular mechanism of Rho-kinase inhibitor.Methods 54 female Lewis rats was immunized with the component of Synthetic PNS myelin sheath protein P2 53-78aa and Freund's complete adjuvant, and Rho-kinase inhibitor Fasudil(25mg/kg.d) were injected intraperitoneally daily from 2 days before antigen immunization. The clinical signs of rats and the histopathology were evaluated. The rats were sacrificed at 9days, 17days, 26days after immunized.Ox40 and OX40L mRNA was detected by RT-PCR which come from spleens, sciatic nerves, peripheral blood mononuclear cells and lymphonodes.Results The peak of clinical course come on 17d p.i in EAN, the mRNA expression of OX40/OX40L was higher on 9d and 17d than 26d.p.i(p<0.05),there was significance difference between the EAN group and CFA control group at the three time point(P<0.05);The demyelination and inflammation cells infiltrating was ameliorated in spinal nerve,The clinical scores in fasudil-treatment group was decereased significantly compared with EAN group(p<0.01);The mRNA expression of OX40 and OX40L in fasudil-treatment group was lower than EAN group at the three time point(p<0.05).CFA group didn't show any clinical manifestation.Conclusions OX40 and OX40L may play a role in the pathogenesis of EAN by taking part in inducing and effect stage. Rho-kinase inhibitor may ameliorate the development of EAN through inhabiting the OX40 and OX40L activation. |
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