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碘海醇对血脑屏障通透性及紧密连接蛋白 ZO-1/Occludin 表达的动态影响。

Dynamic Effects of Ioversol on the Permeability of the Blood-Brain Barrier and the Expression of ZO-1/Occludin in Rats.

机构信息

Department of Neurology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, No.157 XiWuLu Street, Xi'an, 710004, Shaanxi, China.

出版信息

J Mol Neurosci. 2019 Jun;68(2):295-303. doi: 10.1007/s12031-019-01305-z. Epub 2019 Apr 7.

DOI:10.1007/s12031-019-01305-z
PMID:30955191
Abstract

Blood-brain barrier (BBB) dysfunction is involved in the pathogenesis of contrast-induced encephalopathy (CIE), which is a rare adverse event following angiography. In this study, we observed the dynamic effect and potential mechanism of ioversol on the BBB in rats. Eighty-one healthy rats were randomly divided into a normal control group (n = 9), ioversol group (n = 36), and 0.9% NaCl group (n = 36); the latter two groups were separately subdivided into four groups based on time points after treatment (0.5, 3, 6, and 24 h) (n = 9/group). Permeability of the BBB was measured by an Evans Blue (EB) assay. Levels of the tight junction (TJ) proteins ZO-1 and occludin were determined by western blot and immunofluorescence staining. EB content increased at 3 h after the administration of ioversol via the carotid artery and reached a peak at 6 h (P < 0.05), whereas it decreased to its normal level at 24 h. Western blot and immunofluorescence staining indicated that the expression of ZO-1 in brain tissues gradually decreased to its lowest level at 3 h, and then increased gradually, but was still lower than that of the normal control group at 24 h (P < 0.05). Occludin was similar, but its lowest expression appeared at 0.5 h. This study demonstrated that the permeability of BBB in rats increased first and then decreased after ioversol was injected into the carotid artery. The mechanism may be related to altered protein expression of TJs, which are important structures in BBB. Early intervention against TJ proteins may be an effective measure to prevent and treat CIE.

摘要

血脑屏障(BBB)功能障碍与对比剂诱导性脑病(CIE)的发病机制有关,CIE 是血管造影后罕见的不良反应。在这项研究中,我们观察了碘海醇对大鼠 BBB 的动态作用及潜在机制。81 只健康大鼠随机分为正常对照组(n=9)、碘海醇组(n=36)和 0.9%氯化钠组(n=36);后两组根据治疗后时间点(0.5、3、6 和 24 h)进一步分为 4 个亚组(n=9/组)。通过伊文思蓝(EB)测定法测量 BBB 的通透性。通过 Western blot 和免疫荧光染色测定紧密连接(TJ)蛋白 ZO-1 和 occludin 的水平。经颈动脉给予碘海醇 3 h 后 EB 含量增加,并在 6 h 时达到峰值(P<0.05),而在 24 h 时恢复至正常水平。Western blot 和免疫荧光染色表明,脑组织中 ZO-1 的表达逐渐降低至 3 h 时的最低水平,然后逐渐升高,但在 24 h 时仍低于正常对照组(P<0.05)。occludin 相似,但最低表达出现在 0.5 h。本研究表明,大鼠颈动脉内注射碘海醇后,BBB 的通透性先增加后降低。其机制可能与 TJ 蛋白表达改变有关,TJ 是 BBB 的重要结构。早期干预 TJ 蛋白可能是预防和治疗 CIE 的有效措施。

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