Structural alterations of tight junctions are associated with loss of polarity in stroke-prone spontaneously hypertensive rat blood-brain barrier endothelial cells
Structural alterations of tight junctions are associated with loss of polarity in stroke-prone spontaneously hypertensive rat blood-brain barrier endothelial cells
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DOI：
10.1016/s0006-8993(00)02954-1
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发表时间：
2000-12-08
期刊：
影响因子：
2.9
通讯作者：
Haller, H
中科院分区：
文献类型：
--
作者：
Lippoldt, A;Kniesel, U;Haller, H
易卒中型自发性高血压大鼠（SHRSP）发生卒中的机制尚不清楚。我们检验了SHRSP中风前血脑屏障内皮紧密连接改变的假设。我们通过电子显微镜和免疫细胞化学研究了13周龄SHRSP、自发性高血压卒中抵抗大鼠（SHR）和年龄匹配的Wistar-Kyoto大鼠（WKY）的紧密连接。超薄切片显示SHRSP、SHR和WKY脑毛细血管连接结构无明显差异。然而，使用冷冻断裂法，我们观察到WKY中P面和E面之间紧密连接颗粒的血脑屏障特异性分布（58.7+/-3.6%，P面; 41.2+/-5.59%，E面）。E-face）和SHR（53.2+/-19.3%，P-face; 55.6+/-13.25%，E-face）的脑毛细血管改变为89.4+/-9.9%，SHRSP的脑毛细血管中主要的E-face相关。而紧密连接分子ZO-1、occludin、claudin-1和claudin-5在SHRSP毛细血管中的表达无明显变化。用硝酸镧作示踪剂，SHRSP的脑毛细血管通透性与SHR和WKY相比没有差异。与此相反，分析内皮细胞的极性分布的葡萄糖-1转运蛋白（Glut-1）显示，其近腔：腔的比例从4：1在SHR和WKY减少到1：1在SHRSP的脑毛细血管内皮细胞。总之，我们证明了高血压相关中风的遗传模型中脑毛细血管存在早期变化。我们认为SHRSP血脑屏障内皮细胞紧密连接的栅栏功能紊乱可能导致极性的微妙变化。这些变化可能参与了脑卒中的发病机制。(C)2000 Elsevier Science B. V.保留所有权利。
The mechanisms leading to stroke in stroke-prone spontaneously hypertensive rats (SHRSP) are not well understood. We tested the hypothesis that the endothelial tight junctions of the blood-brain barrier are altered in SHRSP prior to stroke. We investigated tight junctions in 13-week-old SHRSP, spontaneously hypertensive stroke-resistant rats (SHR) and age-matched Wistar-Kyoto rats (WKY) by electron microscopy and immunocytochemistry. Ultrathin sections showed no difference in junction structure of cerebral capillaries from SHRSP, SHR and WKY, respectively. However, using freeze-fracturing, we observed that the blood-brain barrier specific distribution of tight junction particles between P- and E-face in WKY (58.7+/-3.6%, P-face; 41.2+/-5.59%. E-face) and SHR (53.2+/-19.3%, P-face; 55.6+/-13.25%, E-face) was changed to an 89.4+/-9.9% predominant E-face association in cerebral capillaries from SHRSP. However, the expression of the tight junction molecules ZO-1, occludin, claudin-1 and claudin-5 was not changed in capillaries of SHRSP. Permeability of brain capillaries from SHRSP was not different compared to SHR and WKY using lanthanum nitrate as a tracer. In contrast, analysis of endothelial cell polarity by distribution of the glucose-1 transporter (Glut-1) revealed that its abluminal:luminal ratio was reduced from 4:1 in SHR and WKY to 1:1 in endothelial cells of cerebral capillaries of SHRSP. In summary, we demonstrate that early changes exist in cerebral capillaries from a genetic model of hypertension-associated stroke. We suggest that a disturbed fence function of the tight junctions in SHRSP blood-brain barrier endothelial cells may lead to subtle changes in polarity. These changes may contribute to the pathogenesis of stroke. (C) 2000 Elsevier Science B.V. All rights reserved.