Effects Of Prostaglandin E2EP4 Receptor Antagonist On Rat Experimental Autoimmune Neuritis

ObjectivesTo investigate effects of prostaglandin E2EP4 receptor antagonist on rat experimental autoimmune neuritis(EAN), to find new treatments for Guillain-Barre syndrome(GBS).MethodsEighteen female Lewis rats, 7-8 weeks old, were used in the present study, induction and clinical evaluation of EAN, according to random number table, eighteen rats were divided into treatment group A, treatment group B and EAN group(n=6), treatment group A were intraperitoneally injected daily with L161982 before immunization to eight days after immunization, treatment group B were intraperitoneally injected daily with L161982 from days 5 to 16 after immunization, and EAN group was intraperitoneally injected with the same volume L161982 dissolvent, histopathology and RT-PCR examinations, by CCK8 method of in vitro lymphocyte proliferation was measured.ResμLts1.All rats happened EAN, teatment group A and treatment group B displayed a significant delay in onset than EAN group(P<0.05), treatment group A also displayed disease onset than treatment group B(P<0.05), treatment group A disease peak of clinical scores were significantly lower than treatment group B and EAN group(P<0.05).2.Sciatic perivascμLar demyelination of treatment group A and treatment group B was significantly reduced than the EAN group(P<0.05), histological scores was significantly decreased than the EAN group(P<0.05), the number of inflammatory cells of disease peak of the sciatic nerve in treatment group A and treatment group B was significantly less than the EAN group(P<0.05), the number of inflammatory cells of disease peak of the sciatic nerve in treatment group A was also significantly less than treatment group B(P<0.05).3.Treatment group A and treatment group B in the inhibition of BPM, PHA and Con A-induced lymphocyte proliferation was better than the EAN group(P<0.05).4.Treatment group A and treatment group B disease peak of the sciatic nerve inflammatory cytokines TNF-α, IFN-γ, IL-6, IL-17 was significantly less than the EAN group(P<0.05), treatment group A disease peak of the sciatic nerve inflammatory cytokines TNF-α, IFN-γ, IL-6, IL-17 was significantly less than treatment group B(P <0.05).Conclusions1.L161982 was administered to EAN rats on the immunization phase and onset phase can lower peak clinical score, display significant delay in onset, these data suggest that L161982 has therapeutic potential for al eviating EAN.2.Rats treated with L161982 at the both phases significant decreased inflammatory cell infiltration in the sciatic nerve, reduce sciatic inflammatory cytokines TNF-α, IFN-γ, IL-6, IL 17 expression, these data suggest that L161982 can over-expression of pro-inflammatory cytokines.3.Immunization phase treatment group significantly delay the time of onset of EAN, reduced the peak period of the disease clinical scores compared with the onset phase of the treatment group, These suggest that the immunization phase application of PGE2EP4 receptor antagonist L161982 treatment effect is superior to the onset phase.