[ ABSTRACT] AIM:To study the effect of idazoxan ( IDA) on the permeability of blood-brain barrier ( BBB) and the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in mouse ex-perimental autoimmune encephalomyelitis (EAE).METHODS: Female C57BL/6 mice (n=36) were randomly divided into control group, EAE group and IDA group, with 12 mice in each group.EAE was induced by myelin oligodendrocyte glycoprotein 35-55 ( MOG35-55 ) .IDA (2 mg/kg, ip, bid) was administered for 15 d after immunization.The neurological defects of the mice were observed daily and scored.The pathological changes were observed under microscope with HE stai-ning and LFB myelin staining.The BBB permeability was detected by Evans blue extravasation.The expression of MMP-9 and TIMP-1 in the brain of EAE mice was determined by Western blotting.RESULTS: Compared with EAE group, the score of neurological defects in IDA group was decreased, the inflammation was relieved, the BBB permeability was re-duced, and the expression MMP-9 and the ratio of MMP-9/TIMP-1 were decreased ( P<0.05 ) .CONCLUSION: The neuroprotective effect of IDA on mouse EAE might be related to the down-regulation of MMP-9 and the ratio of MMP-9/TIMP-1, thus reducing the degradation of BBB and the permeability of BBB, and ameliorating the pathologic process of EAE.%目的：观察咪唑克生（ idazoxan，IDA）对小鼠实验性自身免疫性脑脊髓炎（ experimental autoimmune encephalomyelitis， EAE）时血脑屏障（ BBB）通透性及脊髓内的MMP-9／TIMP-1表达的影响。方法：选用36只8周左右的C57BL／6小鼠，随机分为空白对照组、EAE组和IDA干预组，每组12只，采用髓鞘少突胶质细胞糖蛋白35-55（ MOG35-55）诱导经典EAE模型，干预组采用IDA 2 mg／kg腹腔注射，每天2次，共15 d。观察每组大鼠发病情况并进行神经功能障碍评分，采用HE染色和LFB髓鞘染色观察病理改变，采用伊文思蓝荧光定量方法检测BBB通透性的变化，并用Western blotting法检测MMP-9和TIMP-1的表达。结果：空白对照组无一发病，与EAE组比较， IDA干预组神经功能障碍评分明显下降，炎性病灶明显减少，BBB通透性明显降低，MMP-9的表达和MMP-9／TIMP-1比值明显下降，差异有统计学意义（P＜0.05）。结论：IDA可能通过下调MMP-9，降低MMP-9／TIMP-1比值，减轻血脑屏障的降解破坏，从而稳固BBB，降低BBB通透性，减缓小鼠EAE的发病。
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