ONO-4817对实验性变态反应性脑脊髓炎的治疗作用

 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-4817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-4817，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-4817能显著改善EAE临床症状(P＜0.01)，同时明显抑制T淋巴细胞增殖(P＜0.01)，显著降低大鼠血清TNFα水平(P＜0.05)。结论研究表明，ONO-4817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。

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

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).METHOD SThe 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).CONCLUSION SONO 4817 reduced the blood brain barrier (BBB) breakdown,inflammatory cell recruitment,and myelin sheath damage significantly and therefore effectively ameliorated EAE in rats.