mPGES-1-PGE2信号通路在视神经脊髓炎发病中的作用及机制研究

视神经脊髓炎（NMO）是一种抗体依赖的星形胶质细胞（ASC）介导的自身免疫性炎性脱髓鞘疾病。既往研究表明花生四烯酸（AA）的COX-2-mPGES-1-PGE2-EPs代谢通路中mPGES-1抑制剂可以缓解多种自身免疫性疾病的临床症状，但在NMO中作用尚不清楚。ASC是PGE-2的主要来源和炎症效应的主要细胞，本课题组前期对NMO-ON患者脑脊液蛋白质谱分析结果提示AA COX-2通路处于明显激活状态，PGE-2表达水平增高；基于以上研究基础，我们提出mPGES-1-PGE2信号通路在NMO疾病进展中发挥重要作用；本课题拟在患者水平进一步验证其在NMO发病中的作用；通过体内实验将COX-2及mPGES-1抑制剂应用于该模型，观察动物行为学及组织病理学变化，应用PCR、流氏细胞术等方法检测通路相关信号分子、炎性因子的改变，以期为NMO的发病机制及mPGES-1抑制剂在NMO中的应用提供基础。

Neuromyelitis Optica (NMO) is an autoimmune inflammatory demyelinating disease, which was caused by antibody-mediated astrocyte (ASC) injury. The recently published study indicated that COX-2-mPGES-1-PGE2-Eps in arachidonic acid (AA) metabolic pathway played an important role and mPGES-1 blocker could attenuate the clinical symptoms of a few autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis. But it is not clear about the effect on NMO. ASC is the major source of PGE-2 and important cell of inflammation. In the previous research, we found that COX-2 pathway of AA had been activated in the acute course of NMO by protein map and the level of PGE-2 improved. Based on the above, we hypothesized that mPGES-1-PGE2 may have a vital role in the incidence of NMO. This study plan to certificate the important role of PGE-2 in NMO in the patient study. And by establishing animal model of NMO with the use of COX-2 and mPGES-1 blocker, we evaluate the animal behavioral performance, histopathological features and levels of important relevant protein, inflammatory factors in this pathway by RT-PCR or Flow Cytometry, in order to interpret the pathogenic mechanisms of mPGES-1-PGE2 in NMO and provide evidence for mPGES-1 blocker application in NMO.