咪唑克生对实验性变态反应性脑脊髓炎小鼠血脑屏障紧密连接的影响

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (2): 138-144.

咪唑克生对实验性变态反应性脑脊髓炎小鼠血脑屏障紧密连接的影响

王新施, 方恢林, 朱振国, 朱攀, 曾庆意, 郑荣远

温州医科大学附属第一医院神经内科,温州 325000,浙江

收稿日期:2014-08-29 修回日期:2014-12-29 出版日期:2015-02-26 发布日期:2015-03-20
通讯作者: 郑荣远,男,学士,教授,博士生导师,研究方向:神经病学,神经药理学。Tel: 13695762600 E-mail: zhengry2013@163.com
作者简介:王新施,女,硕士,主治医师,讲师,研究方向:神经病学。Tel: 13757897051 E-mail: wang_xinshi@163.com
基金资助:
浙江省自然科学基金项目(LQ12H09002);国家自然科学基金项目(81070960)

Effect of idazoxan on the tight junctions of blood-brain barrier in mouse experimental autoimmune encephalomyelitis

WANG Xin-shi, FANG Hui-lin, ZHU Zhen-guo, ZHU Pan, ZENG Qing-yi, ZHENG Rong-yuan

Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

Received:2014-08-29 Revised:2014-12-29 Online:2015-02-26 Published:2015-03-20

摘要/Abstract

摘要： 目的: 观察咪唑克生(idazoxan,IDA)对实验性变态反应性脑脊髓炎(experimental autoimmune encephalomyelitis, EAE)小鼠的血脑屏障(blood-brain barrier, BBB)紧密连接的影响。方法: 选用36只8周的C57BL/6小鼠,随机分为空白对照组、EAE组和IDA干预组各12只,采用MOG_35-55诱导经典EAE模型,干预组采用IDA 2 mg/kg 腹腔注射、每天两次、共15 d。观察每组大鼠发病情况并进行神经功能缺损评分,采用HE染色和LFB髓鞘染色方法观察病理改变,采用伊文思蓝荧光定量方法检测BBB通透性的变化,透射电镜观察BBB紧密连接超微结构,并用Western blot检测BBB紧密连接蛋白ZO-1、Occludin、Claudin-5、JAM-1的表达。结果: 空白对照组动物无一发病,与EAE组比较, IDA干预组神经功能缺损评分明显下降,炎性病灶和脱髓鞘病灶明显减少,BBB通透性明显降低,BBB超微结构的破坏明显减轻,BBB紧密连接相关蛋白ZO-1、Claudin-5的表达明显升高,差异具有统计学意义(P<0.05)。结论: IDA可能通过上调血脑屏障紧密连接蛋白ZO-1和Claudin-5的表达从而减轻EAE时的血脑屏障破坏而发挥对EAE小鼠的神经保护作用。

关键词: 咪唑克生, 血脑屏障, 紧密连接, 实验性变态反应性脑脊髓炎, 小鼠

Abstract: AIM: To study the effect of idazoxan(IDA)on the tight junctions of blood-brain barrier (BBB) in mouse experimental autoimmune encephalomyelitis (EAE) and the molecular mechanism.METHODS: Thirty six female C57BL/6 mice were randomly ascribed to control group, EAE group and IDA group, with 12 mice in each group. EAE was induced by MOG35-55. IDA (2 mg/kg, i.p., bid) was administrated for 15 days after MOG immunization. The signs of neurological defects of the mice were observed daily and scored, the pathological changes were observed, the BBB permeability were detected by Evan's blue extravasation, the ultrastructure of BBB were observed by transmission electron microscopy, and the expressions of BBB tight junction proteins (ZO-1,Claudin-5, Occludin, and JAM-1) in the brain of EAE mice were detected by Western blot analysis.RESULTS: Compared with EAE group, the score of neurological defects in IDA group was decreased, the pathological change and the ultrastrucuture of BBB destroy seen under the electron microscope was relieved, the BBB permeability was reduced, and the expressions of ZO-1 and Claudin-5 were increased (P<0.05).CONCLUSION: IDA possess neuroprotective effect on mouse EAE and ameliorate the dysfunction of BBB during EAE, whose effect might be related to the upregulation of the tight junction proteins ZO-1 and Claudin-5.

Key words: idazoxan, blood-brain barrier, tight junction, experimental autoimmune encephalomyelitis, mice

中图分类号:

R965.2

王新施, 方恢林, 朱振国, 朱攀, 曾庆意, 郑荣远. 咪唑克生对实验性变态反应性脑脊髓炎小鼠血脑屏障紧密连接的影响[J]. 中国临床药理学与治疗学, 2015, 20(2): 138-144.

WANG Xin-shi, FANG Hui-lin, ZHU Zhen-guo, ZHU Pan, ZENG Qing-yi, ZHENG Rong-yuan. Effect of idazoxan on the tight junctions of blood-brain barrier in mouse experimental autoimmune encephalomyelitis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(2): 138-144.

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