前列腺素E2EP4受体拮抗剂对大鼠实验性自身免疫性神经炎的影响

发布时间：2017-12-28 22:22

本文关键词：前列腺素E2EP4受体拮抗剂对大鼠实验性自身免疫性神经炎的影响　出处：《苏州大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的探讨前列腺素E2EP4受体拮抗剂对大鼠实验性自身免疫性神经炎(EAN)的影响,为吉兰-巴雷综合征(GBS)寻找新的治疗方法。方法选取7~8周龄雌性大鼠18只,建立EAN模型,进行临床评分,按照随机数字表法分成治疗A组、治疗B组和EAN组各6只,治疗A组在免疫前1d至免疫后8d腹腔注射前列腺素E2EP4受体拮抗剂L161982,治疗B组在免疫后5~16d腹腔注射L161982,EAN组腹腔注射相同体积的L161982溶媒DMSO+PBS,进行组织病理学检查和逆转录聚合式酶联反应(RT-PCR)技术检测,通过CCK8法对体外淋巴细胞增殖进行测定。结果1.所有大鼠均发生EAN,且治疗A组和治疗B组发病时间与EAN组比较明显延迟(P0.05),治疗A组与治疗B组比较发病时间明显延迟(P0.05);治疗A组疾病高峰期临床评分明显低于治疗B组和EAN组(P0.05)。2.治疗A组和治疗B组坐骨神经血管周围髓鞘脱失较EAN组明显减轻(P0.05),组织学评分较EAN组明显减少(P0.05),治疗A组和治疗B组疾病高峰期大鼠淋巴结炎性细胞浸润数目明显少于EAN组(P0.05),治疗A组大鼠淋巴结炎性细胞浸润数目明显少于治疗B组(P0.05)。3.治疗A组和治疗B组在抑制BPM、PHA和ConA诱导的淋巴细胞增殖方面明显优于EAN组(P0.05)。4.治疗A组和治疗B组疾病高峰期大鼠淋巴结炎性细胞因子TNF-α、IFN-γ、IL-6、IL-17明显少于EAN组(P0.05),治疗A组大鼠淋巴结炎性细胞因子TNF-α、IFN-γ、IL-6、IL-17明显少于治疗B组(P0.05)。结论1.采用L161982治疗EAN,无论是在免疫阶段还是发病阶段,均能够明显降低高峰期临床评分,延迟EAN发病时间,提示L161982能够治疗EAN。2.采用L161982治疗EAN,无论是在免疫阶段还是发病阶段,均能够减少淋巴结炎性细胞浸润数目,降低淋巴结炎性细胞因子TNF-α、IFN-γ、IL-6、IL-17表达,提示L161982能够抑制细胞免疫反应。3.L161982治疗免疫阶段延迟EAN发病时间和疾病高峰期临床评分明显优于治疗发病阶段,提示前列腺素E2EP4受体拮抗剂应用于免疫阶段效果优于发病阶段。
[Abstract]:Objective to investigate the prostaglandin E2EP4 receptor antagonist on rat experimental autoimmune neuritis (EAN) effect for Guillain Barre syndrome (GBS) looking for new treatment methods. Methods 7~8 week old female 18 rats to establish EAN model, clinical score, were randomly divided into treatment group A, treatment group B and EAN group with 6 rats in each treatment group A in immune 1D before and 8D after immunization by intraperitoneal injection of prostaglandin E2EP4 receptor antagonist L161982, treatment group B in immune after intraperitoneal injection of 5~16d L161982, EAN group was intraperitoneally injected with the same volume of L161982 solvent DMSO+PBS, histopathological examination and polymerase chain reaction (RT RT-PCR) detection on lymphocyte proliferation in vitro was determined by CCK8 method. Results 1. all the rats developed EAN, and the time of onset in group A and group B was significantly longer than that in group EAN (P0.05). The time of onset in the treatment group was significantly delayed compared with that in the treatment group (P0.05), and the clinical score in the treatment group was significantly lower than that in the treatment group and the EAN group (A). 2. treatment group A and treatment group B sciatic nerve demyelination around blood vessels significantly reduced compared with EAN group (P0.05), histological score was less than that in group EAN (P0.05), inflammatory cells in treatment group A and treatment group B disease peak rat invasion number was significantly less than in group EAN (P0.05), inflammatory cells in the treatment of A group of rats was significantly less than the number of invasive treatment group B (P0.05). 3. in group A and group B, the proliferation of lymphocytes induced by BPM, PHA and ConA was significantly better than that in group EAN (P0.05). 4., in the A group and the B group, the inflammatory cytokines TNF-, IFN-, IL-6 and IL-17 were significantly less than those in the EAN group (P0.05) at the peak stage of the disease, and the inflammatory cytokines in the A group were significantly less than those in the treatment group. Conclusion 1. the use of L161982 in the treatment of EAN, both in the immune stage or in the onset stage, can significantly reduce the peak clinical score and delay the onset time of EAN, suggesting that L161982 can treat EAN. 2., using L161982 to treat EAN, both in the immune stage or in the onset stage, can reduce the number of inflammatory cell infiltration and decrease the expression of TNF-, IFN-, IL-6 and IL-17, suggesting that L161982 can inhibit the cellular immune response. 3.L161982 treatment delayed the onset time of EAN and the peak of disease. The clinical score was significantly better than that of the treatment stage, suggesting that the prostaglandin E2EP4 receptor antagonist used in the immune stage is better than the onset stage.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R745.43

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