前列腺素E2-EP4受体拮抗剂对大鼠实验性自身免疫性神经炎的作用

目的   探讨前列腺素E2-EP4受体拮抗剂L161982对大鼠实验性自身免疫性神经炎(EAN)的作用及其机制。方法   用牛周围神经髓磷脂(BPM)抗原乳剂免疫大鼠制备EAN模型。将21只Lewis大鼠随机分为治疗A组、治疗B组和对照组，治疗A组于免疫前1天至免疫后第8天(免疫阶段)每日腹腔注射 L161982(5mg/kg)，治疗B组于免疫后第5至16天(发病阶段)每日腹腔注射 L161982(5mg/kg)，对照组每日腹腔注射相同体积的L161982溶媒。观察各组发病时间和临床评分，于疾病高峰期(免疫后第16天)行坐骨神经组织病理学检查，免疫组化法检测坐骨神经中IFN-γ、IL-17表达，细胞计数试剂CCK-8法检测引流淋巴结淋巴细胞增殖反应。 结果   与对照组比较，治疗A组和治疗B组均能延迟EAN发病时间(P<0.05)，减少坐骨神经炎性细胞浸润数目(P<0.05)和IFN-γ、IL-17表达(P<0.05)，抑制BPM刺激T淋巴细胞增殖反应(P<0.05)。治疗A组疾病高峰期临床评分明显低于治疗B组和对照组(P<0.05)。结论   L161982可能通过抑制促炎性细胞因子IFN-γ、IL-17过度表达和自身反应性T淋巴细胞增殖减轻EAN病情，免疫阶段应用L161982具有更明显的治疗效果。

Effects of prostaglandin E2-EP4 receptor antagonist on rat experimental autoimmune neuritis

Objective   To explore the role of L161982, one  prostaglandin E2-EP4 receptor antagonist, and its mechanism in rat experimental autoimmune neuritis (EAN). Methods   The rats were injected with bovine peripheral nerve myelin(BPM) antigen emulsion to prepare EAN model. Twenty-one Lewis rats were randomly divided into treatment group A, treatment group B and control group. Treatment group A were intraperitoneally injected daily with L161982(5mg/kg) from one day before immunization to the eighth day after immunization (immunization phase). Treatment group B were intraperitoneally injected daily with L161982(5mg/kg) from the fifth to sixteenth day after immunization (onset phase), and control group were intraperitoneally injected with the same volume of L161982 dissolvent. The effects were assessed in terms of appearance of clinical signs, clinical score, histopathology, and IFN-γ and IL-17 expressions in sciatic nerve sections, and the draining lymph nodes lymphocyte proliferative response was detected by cell counting kit-8(CCK-8). Results   Treatment group A and treatment group B displayed a significant delay in the onset of EAN (P＜0.05), a decreased inflammatory cell infiltration into the sciatic nerve(P＜0.05), decreased numbers of IFN-γ and IL-17 expressions in the sciatic nerve(P＜0.05), and reduced BPM stimulated T lymphocyte proliferative responses(P＜0.05) compared to the control group. Only treatment group A had decreased peak clinical score(P＜0.05). Conclusion   L161982 ameliorates the severity of EAN, presumably by moderating the over-expression of proinflammatory cytokines and suppressing self-reactive T lymphocyte proliferation. The immunization phase has a more significant therapeutic effect.