咪唑克生对EAE小鼠血脑屏障通透性及对MMP-9/TIMP-1的影响  

Effect of idazoxan on permeability of blood-brain barrier and expression of MMP-9/TIMP-1 in mouse experimental autoimmune encephalomyelitis

作　　者：王新施[1] 曾庆意[1] 朱振国[1] 朱攀[1] 徐惠琴[1] 郑荣远[1] 

机构地区：[1]温州医科大学附属第一医院神经内科,浙江温州325000

出　　处：《中国病理生理杂志》2014年第12期2254-2258,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81070960);浙江省自然科学基金资助项目(No.LQ12H09002)

摘　　要：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。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 （MOG3~_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.

关 键 词：咪唑克生 血脑屏障 基质金属蛋白酶9 组织型基质金属蛋白酶抑制物1 实验性自身免疫性脑脊髓炎 

分 类 号：R363[医药卫生—病理学] R774.51[医药卫生—基础医学]