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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(5 mg/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(5 mg/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。
Objective To investigate the effect of prostaglandin E2-EP4 receptor antagonist L161982 on experimental autoimmune neuritis (EAN) and its mechanism. Methods EAN model was prepared by immunization of rats with bovine peripheral nerve myelin (BPM) antigen emulsion. Twenty-one Lewis rats were randomly divided into treatment A group, treatment B group and control group. In treatment A group, L161982 (5 mg / kg) was intraperitoneally injected from day 1 before immunization to day 8 after immunization (immunization phase) Group B received daily intraperitoneal injections of L161982 (5 mg / kg) on days 5 to 16 after immunization (onset stage), and control group received daily intraperitoneal injections of the same volume of L161982 vehicle. The onset time and clinical score of each group were observed. The sciatic nerve histopathological examination was performed at the peak of the disease (16 days after immunization). The expression of IFN-γ and IL-17 in the sciatic nerve was detected by immunohistochemistry. The CCK-8 Detection of drainage lymph node lymphocyte proliferation response. Results Compared with the control group, both treatment group A and treatment group B could delay the onset of EAN (P <0.05) and reduce the number of inflammatory cells (P <0.05) and the expression of IFN-γ and IL-17 ) Inhibited BPM-stimulated T lymphocyte proliferation (P <0.05). The clinical score of treatment group A at the peak of disease was significantly lower than that of treatment B and control group (P <0.05). Conclusion L161982 may alleviate EAN by inhibiting the over-expression of proinflammatory cytokines IFN-γ, IL-17 and autoreactive T lymphocyte proliferation. L161982 has a more significant therapeutic effect during the immunization phase.