Apotropaic And Therapeutical Effect Of Apelin-13on The Experimental Autoimmune Neuritis And The Mechanism Possible In Experimental Autoimmune Neuritis Rats

Objective To observe the apotropaic and therapeutical effect of Apelin-13on the experimental autoimmune neuritis and to explore the mechanism possible in experimental autoimmune neuritis (EAN) rats.Methods The rats models of EAN were established by injection of peripheral nerve myelin sheath antigen (P257-81) in the foot pad of male Lewis rats. The rats were randomly divided into the control, EAN model, and Apelin-13treatment group. The rats in Apelin-13treatment group were injected with Apelin-13(0.1mg/kg) by tail vein once daily from the first day to the fifteenth day. The clinical incidence and pathology in the rats were assessed. The infiltration of inflammatory cells in sciatic nerve was observed. The cell suspensions of plenic lymphocytes were prepared. The cell proliferation was tested by flow cytometry. The level of blood plasma tumor necrosis factor-a (TNF-α)、interleukin-6(IL-6)、interferon-y (IFN-γ)、interleukin-4(IL-4) and transforming growth factor-β(TGF-β) were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of TNF-α、IL-6、IFN-γ、IL-4and TGF-β in lymph node were measured by Real-time PCR and Western blot respectively.Results (1) The infiltration of inflammatory cells and focal demyelination in the nerve bundles of sciatic nerve were observed in EAN model group. Compared with the control group, the basal level of proliferation, the level of proliferation induced by LPS and peripheral nerve myelin sheath antigen (P257-81) were significantly increased in EAN model group (all P<0.05). Compared with the control group, the level of blood plasma TNF-α、IL-6and IFN-γ were significantly increased and the level of blood plasma IL-4and TGF-P were significantly decreased in EAN model group (all P<0.05). Compared with the control group, the expressions of TNF-α、IL-6and IFN-γ in lymph node were significantly increased and the expressions of IL-4and TGF-β were significantly decreased in EAN model group (all P<0.05).(2) Compared with the EAN model group, the initial time of nervous symptom was significantly increased, the maximal neurological score was significantly decreased, the infiltration of inflammatory cells and focal demyelination in the nerve bundles of sciatic nerve were significantly decreased in the Apelin-13treatment group (all P<0.05). Compared with the EAN model group, the basal level of proliferation, the level of proliferation induced by LPS and peripheral nerve myelin sheath antigen (P257-81) were significantly decreased in the Apelin-13treatment group (all P<0.05). Compared with the EAN model group, the level of blood plasma TNF-α、IL-6and IFN-γ were significantly decreased and the level of blood plasma IL-4and TGF-β were significantly increased in the Apelin-13treatment group (all P<0.05). Compared with the EAN model group, the expressions of TNF-α、IL-6and IFN-γ in lymph node were significantly decreased and the expressions of IL-4and TGF-β were significantly increased in the Apelin-13treatment group (all P<0.05).Conclusion Apelin-13can prevent and cure the EAN in EAN rats model, the mechanism of which may be related with up-regulation of TNF-α、IL-6and IFN-γ and down-regulation of IL-4and TGF-β.11figures,8tables,73references.