ONO-4817对实验性变态反应性脑脊髓炎的治疗作用  

Suppression of active experimental autoimmune encephalomyelitis in Lewis rats by using compound ONO-4817,a new inhibitor of matrix metalloprot einases

作　　者：吕佩源[1] 宋春风[2] 高昌星[3] 井上敦[3] 

机构地区：[1]河北省人民医院神经内科,河北石家庄050051 [2]河北医科大学电镜实验中心,河北石家庄050017 [3]日本信州大学附属病院第三内科,日本长野县松本市3908621

出　　处：《中国药学杂志》2003年第1期28-31,共4页Chinese Pharmaceutical Journal

摘　　要：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对实验性变态反应性脑脊髓炎(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 ,又可以抑制炎细胞浸润和髓鞘破坏 ,从而有效缓解EAE。OBJECTIVE: To explore the effects of ONO-4817, a new synthetic hydroxamic acid-based combined inhibitor of matrix metalloproteinases (MMPs) ativity, on experimental autoimmune encephalomyelitis (EAE). METHODS: The rats with EAE were treated after oral administration of ONO-4817 and then were examined for the development of neurological sign, T cell proliferative responses and serum tumor necrosis factor (TNF)-α concentrations respectively. RESULTS: The clinical signs were suppressed significantly in ONO-4817 group(P<0.01). T cell proliferation was significantly inhibited (P<0.01) and the serum TNF-α concentration was significantly decreased (P<0.05). CONCLUSIONS: ONO-4817 reduced the blood-brain barrier (BBB) breakdown, inflammatory cell recruitment, and myelin sheath damage significantly and therefore effectively ameliorated EAE in rats.

关 键 词：多发性硬化 实验性变态反应性脑脊髓炎 基质金属蛋白酶抑制剂 T淋巴细胞增殖 肿瘤坏死因子-Α 

分 类 号：R744.5[医药卫生—神经病学与精神病学]