Hypertonic saline alleviates experimentally induced cerebral oedema through suppression of vascular endothelial growth factor and its receptor VEGFR2 expression in astrocytes.
Hypertonic saline alleviates experimentally induced cerebral oedema through suppression of vascular endothelial growth factor and its receptor VEGFR2 expression in astrocytes.
复制标题
高渗盐水通过抑制星形胶质细胞中血管内皮生长因子及其受体 VEGFR2 的表达减轻实验诱导的脑水肿
DOI：
10.1186/s12868-016-0299-y
复制
发表时间：
2016-10-13
期刊：
影响因子：
2.4
通讯作者：
Zeng H
中科院分区：
文献类型：
--
作者：
Huang L;Cao W;Deng Y;Zhu G;Han Y;Zeng H
脑水肿与血脑屏障通透性密切相关，血管内皮生长因子（VEGF）及其受体血管内皮生长因子受体2（VEGFR 2）是血脑屏障通透性的重要调节因子。封闭小带1（ZO-1）和claudin-5也是血脑屏障的重要组成部分。高渗盐水被广泛用于减轻脑水肿。本研究旨在探讨高渗盐水有效改善脑水肿的可能机制。本研究采用SD大鼠大脑中动脉闭塞（MCAO）模型和原代星形胶质细胞缺氧缺糖模型。以脑含水量（BWC）为指标评价10%HS对脑水肿的影响.以伊文思蓝（EB）外渗量评价10%HS对血脑屏障的保护作用。通过对VEGF、VEGFR 2、ZO-1和claudin-5的定量分析，阐明10%HS改善脑水肿的机制。用干湿比法测定脑组织含水量，10%HS治疗后脑组织含水量明显降低（P < 0.05）。我们还研究了10%HS对血脑屏障的保护作用，其有效地减少了缺血周围脑组织中EB的外渗。10%HS处理后，缺血24 h脑组织VEGF和VEGFR 2的mRNA和蛋白表达明显下调（P < 0.05）。沿着体外研究显示，缺氧条件下原代星形胶质细胞VEGF和VEGFR 2 mRNA和蛋白表达增加（P < 0.05），HS处理后VEGF和VEGFR 2 mRNA和蛋白表达受到抑制（P < 0.05）。此外，HS还能有效抑制ZO-1、claudin-5的下调。结果表明，10%HS可能通过抑制VEGF-VEGFR 2介导的ZO-1、claudin-5的下调而降低缺血诱导的BBB通透性，从而减轻脑水肿。
Cerebral oedema is closely related to the permeability of blood–brain barrier, vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) all of which are important blood–brain barrier (BBB) permeability regulatory factors. Zonula occludens 1 (ZO-1) and claudin-5 are also the key components of BBB. Hypertonic saline is widely used to alleviate cerebral oedema. This study aimed to explore the possible mechanisms underlying hypertonic saline that ameliorates cerebral oedema effectively. Middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and of oxygen–glucose deprivation model in primary astrocytes were used in this study. The brain water content (BWC) was used to assess the effect of 10 % HS on cerebral oedema. The assessment of Evans blue (EB) extravasation was performed to evaluate the protective effect of 10 % HS on blood–brain barrier. The quantification of VEGF, VEGFR2, ZO-1 and claudin-5 was used to illustrate the mechanism of 10 % HS ameliorating cerebral oedema. BWC was analysed by wet-to-dry ratios in the ischemic hemisphere of SD rats; it was significantly decreased after 10 % HS treatment (P < 0.05). We also investigated the blood–brain barrier protective effect by 10 % HS which reduced EB extravasation effectively in the peri-ischemic brain tissue. In parallel to the above notably at 24 h following MCAO, mRNA and protein expression of VEGF and VEGFR2 in the peri-ischemic brain tissue was down-regulated after 10 % HS treatment (P < 0.05). Along with this, in vitro studies showed increased VEGF and VEGFR2 mRNA and protein expression in primary astrocytes under hypoxic condition (P < 0.05), but it was suppressed after HS treatment (P < 0.05). In addition, HS inhibited the down-regulation of ZO-1, claudin-5 effectively. The results suggest that 10 % HS could alleviate cerebral oedema possibly through reducing the ischemia induced BBB permeability as a consequence of inhibiting VEGF–VEGFR2-mediated down-regulation of ZO-1, claudin-5.
登录
查看更多内容
DOI：
10.1083/jcb.85.3.890
发表时间：
1980-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
McCarthy KD;de Vellis J
通讯作者：
de Vellis J
DOI：
10.1186/cc11670
发表时间：
2012-10-04
期刊：
Critical care (London, England)
影响因子：
--
作者：
Cao C;Yu X;Liao Z;Zhu N;Huo H;Wang M;Ji G;She H;Luo Z;Yue S
通讯作者：
Yue S
影响因子：
5.3
作者：
Huang, Ping;Zhou, Chang-Man;Han, Jing-Yan
通讯作者：
Han, Jing-Yan
影响因子：
2.9
作者：
Belayev, L;Busto, R;Ginsberg, MD
通讯作者：
Ginsberg, MD
影响因子：
4.4
作者：
Lee, Jae Hoon;Cui, Hui Song;Koo, Bon-Nyeo
通讯作者：
Koo, Bon-Nyeo