天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (12): 1219-1223.doi: 10.11958/20191084

• 实验研究 • 上一篇    下一篇

紧密连接蛋白1在实验性大鼠蛛网膜下腔 出血后脑血管痉挛中的作用

邹敏刚，罗德芳，胡坤，周小平，张震宇△   

  1. 南昌大学附属赣州医院神经外科（邮编341000）
  • 收稿日期:2019-04-15 修回日期:2019-09-15 出版日期:2019-12-15 发布日期:2019-12-15
  • 通讯作者: 张震宇 E-mail:zzyns@163.com
  • 作者简介:邹敏刚（1987），男，硕士，主治医师，主要从事脑血管病研究
  • 基金资助:
    ZO-1蛋白与实验性蛛网膜下腔出血后脑血管痉挛的相关研究

The role of zonula occludens-1 in cerebral vasospasm after experimental subarachnoid hemorrhage in rats

ZOU Min-gang, LUO De-fang, HU Kun, ZHOU Xiao-ping, ZHANG Zhen-yu△   

  1. Department of Neurosurgery, Ganzhou Hospital of Nanchang University, Ganzhou 341000, China
  • Received:2019-04-15 Revised:2019-09-15 Published:2019-12-15 Online:2019-12-15
  • Supported by:
     

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摘要： 目的 观察实验性蛛网膜下腔出血（SAH）后基底动脉壁中紧密连接蛋白1（ZO-1）的表达变化及与脑血管 痉挛（CVS）的相关性。方法 60只健康雄性SD大鼠随机分成SAH组、假注血组，其中SAH组根据不同时间点再分 为1 d、3 d、5 d、7 d、14 d等亚组；利用枕大池二次注血法构建大鼠SAH模型，假注血组仅注入等量生理盐水，每组10 只。HE染色观察基底动脉病理及管壁形态学变化，运用免疫组化染色及Western blot分析基底动脉壁中ZO-1的表 达水平。结果 HE染色光镜下发现SAH组基底动脉均存在不同程度的狭窄及内皮紊乱，其中在SAH 后3 d最为显 著，其管腔内径约为假注血组的44%，管壁厚度约为假注血组的3.5倍，之后基底动脉狭窄程度逐渐降低，至14 d时 大致恢复正常。免疫组化染色及Western blot结果示SAH组基底动脉壁中ZO-1的表达均存在不同程度的下降，其中 在第3 天时降至最低，之后逐渐恢复，至第14 天时基本接近正常。相关性分析表明，ZO-1的表达与基底动脉管腔内 径呈正相关（r=0.719，P＜0.05），与管壁厚度呈负相关（r=-0.686，P＜0.05）。结论 SAH后ZO-1的表达明显下降，下 降趋势与不同时相CVS程度变化相一致，提示ZO-1可能在SAH后CVS的发生过程中发挥重要作用，其机制可能是 通过影响缝隙连接功能，使血管收缩信号传导增强。

关键词: 蛛网膜下腔出血, 血管痉挛, 颅内, 紧密连接蛋白质类, 基底动脉, 紧密连接蛋白1, 机制

Abstract: Objective To investigate the association between zonula occludens-1 (ZO-1) and cerebral vasospasm (CVS) by observing the expressions of ZO-1 in the basilar artery after experimental subarachnoid hemorrhage (SAH) in rats. Methods Total 60 healthy male Sprague-Dawley (SD) rats were randomly divided into 2 groups, SAH group and shaminjection group. Then, the SAH group was divided into 5 subgroups according to time points (1 d, 3 d, 5 d, 7 d and 14 d). Twice autologous arterial blood injection into cistema magna was used to establish SAH model in rats. Moreover, the sham-injection group only accepted an equal volume of normal saline (NS). The expression level of ZO-1 in basilar artery wall was analyzed by immunohistochemistry and Western blot assay. The pathological and wall morphology changes of the basilar artery were observed with HE staining. Results The pathological changes included varying degrees of arterial stenosis and endothelial dysfunction were found by HE staining, and the changes were the most significant on the 3rd day after SAH. The inner luminal diameter was about 44% of the sham-injection group on the 3rd, and the wall thickness was about 3.5 times of the sham-injection group. Then the arterial stenosis began to relief with the progress of time gradually, and it’s nearly normal on the 14th day. The expression of ZO-1 declined in SAH group, and reached the minimum on the 3rd, then gradually recover. On the 14th day, the level was nearly normal. Relativity analysis suggested that the expression of ZO-1 was positively correlated with the inner luminal diameter of the basilar artery (r=0.719, P＜0.05), and negatively correlated with the wall thickness (r=- 0.686, P＜0.05). Conclusion The expression of ZO-1 in the basilar artery decreases after SAH, and there is a consistent relationship between the expression of ZO-1 and the change degree of CVS in the different points, which suggests ZO-1 may be involved in the mechanism of CVS after SAH, and it’s possible to enhance the signal transduction of vasoconstriction by affecting the function of gap junction.

Key words: subarachnoid hemorrhage, vasospasm, intracranial, tight junction proteins, basilar artery, ZO-1；mechanism

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