Objective To explore the clinical effects of ONO-4817, a new synthetic hydroxamic acid-based combined inhibitor of matrix metalloproteinases (MMPs) activity, on experimental autoimmune encephalo-myelitis (EAE). Methods The rats of EAE were treated with ONO-4817 by oral and then were examined for the development of neurological sign, T cell proliferative responses and serum tumor necrosis factor (TNF)-α concentrations. Results The clinical signs were suppressed significantly in ONO-4817 group EAE (P<0.01). Furthermore, T cell proliferation was significantly inhibited (P<0.01) and the serum TNF-α concentration was significantly decreased (P<0.05) in ONO-4817-treated rats. Conclusions By inhibiting of MMPs activities, suppressing T cell proliferation and by decreasing TNF-α production, ONO-4817 would reduce the blood-brain barrier (BBB) breakdown, inflammatory cell recruitment, and myelin sheath damage significantly and therefore efficiently ameliorate EAE.%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对实验性自身免疫性脑脊髓炎(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TNF-α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,又可抑制炎细胞浸润和髓鞘破坏,从而有效缓解EAE.
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