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目的 探讨一种新合成的含氧肟酸的基质金属蛋白酶 ( MMP)抑制剂 ONO-481 7对实验性自身免疫性脑脊髓炎 ( EAE)的治疗效果。方法 给 EAE大鼠口服 ONO-481 7,观察临床症状、T淋巴细胞增殖以及血清肿瘤坏死因子 ( TNF) -α水平。结果 ONO-481 7能显著改善 EAE临床症状 ( P <0 .0 1 ) ,同时明显抑制 T淋巴细胞增殖 ( P <0 .0 1 ) ,显著降低大鼠血清 TNF-α水平 ( P <0 .0 5 )。结论 研究表明 ,ONO-481 7通过抑制 MMPs活性、T淋巴细胞增殖和减少 TNF-α生成 ,进而能显著减轻血脑屏障 ( BBB)的破坏 ,又可抑制炎细胞浸润和髓鞘破坏 ,从而有效缓解 EAE。
Objective To investigate the therapeutic effect of ONO-481 7, a newly synthesized hydroxamic acid-containing matrix metalloproteinase (MMP) inhibitor, on experimental autoimmune encephalomyelitis (EAE). Methods ONO-481 7 was orally administered to EAE rats. Clinical symptoms, T lymphocyte proliferation and serum tumor necrosis factor (TNF) -α were observed. Results ONO-481 7 could significantly improve the clinical symptoms of EAE (P <0.01) and significantly inhibit the proliferation of T lymphocytes (P <0.01) and significantly decrease the level of serum TNF-α (P <0. 0 5). CONCLUSIONS: ONO-481 7 can effectively reduce the damage of the blood-brain barrier (BBB), inhibit the infiltration of inflammatory cells and destroy the myelin sheath by inhibiting the activity of MMPs, the proliferation of T lymphocytes and the production of TNF-α Ease EAE.