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目的研究胞浆塑磷脂酶A_2(cPLA_2)的化学抑制剂对实验性自身免疫性脑脊髓炎(EAE)的影响及相关机制。方法将34只雌性C57BL/6小鼠分为3组(两组干预组各12只及对照组10只),用髓鞘少突胶质细胞糖蛋白35-55多肤诱导建立EAE模型,两组干预组分别用200μL浓度为2mmol/L及4mmol/L的cPLA_2特异性抑制剂—花生四烯酸三氟甲基嗣(AACOCF_3)在免疫当天至免疫后第16天隔日一次给小鼠腹腔内注射,对照组则不采取干预措施,比较各组EAE小鼠临床表现及高峰期病理改变,并用免疫组织化学染色比较各组脊髓中单核细胞趋化蛋白(MCP)-1和巨噬细胞炎性蛋白(MIP)-1α表达的差异。结果两干预组EAE小鼠的临床及病理改变均较对照组显著减轻,干预组小鼠脊髓中cPLA_2、MCP-1,MIP-1α的表达较对照组显著减低,上述改变与AACOCF_3呈剂量依赖性。结论cPLA_2化学抑制剂对EAE有治疗作用,cPLA_2可能参与调节EAE小鼠中枢神经系统中MCP-1及MIP-1α的产生。
Objective To study the effect and mechanism of chemical inhibitors of cytosolic phospholipase A_2 (cPLA_2) on experimental autoimmune encephalomyelitis (EAE). Methods Thirty-four female C57BL / 6 mice were divided into three groups (12 in each group and 10 in control group). EAE model was established by using myelin oligodendrocyte glycoprotein 35-55, The mice in each group were treated with 200μL of AACOCF_3, a specific inhibitor of 2 mmol / L and 4 mmol / L of cPLA 2, respectively, on the day of immunization until the 16th day after immunization. The control group did not take any intervention measures. The clinical manifestations and peak pathological changes of EAE mice in each group were compared. Immunohistochemical staining was used to compare the expression of monocyte chemoattractant protein (MCP) -1 and macrophage inflammatory cell Differences in the expression of MIP-1α. Results The clinical and pathological changes of EAE mice in both intervention groups were significantly reduced compared with those in control group. The expression of cPLA_2, MCP-1 and MIP-1α in spinal cord of mice in intervention group was significantly lower than that in control group. The above changes were in a dose-dependent manner with AACOCF 3 . Conclusion The cPLA 2 chemotherapeutic agents have a therapeutic effect on EAE. CPLA 2 may be involved in the regulation of MCP-1 and MIP-1α production in the central nervous system of EAE mice.