PROTECTIVE EFFECTS OF THROMBOMODULIN ON MICROVASCULAR PERMEABILITY AFTER SUBARACHNOID HEMORRHAGE IN MOUSE MODEL
PROTECTIVE EFFECTS OF THROMBOMODULIN ON MICROVASCULAR PERMEABILITY AFTER SUBARACHNOID HEMORRHAGE IN MOUSE MODEL
复制标题
血栓调节蛋白对小鼠蛛网膜下腔出血后微血管通透性的保护作用
DOI：
10.1016/j.neuroscience.2015.04.058
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发表时间：
2015-07
期刊：
影响因子：
3.3
通讯作者：
Yan J. -H.
中科院分区：
文献类型：
--
作者：
Xu T.;Zhang W. -G.;Sun J.;Zhang Y.;Lu J. -F.;Zhou C. -M.;Han H. -B.;Yan J. -H.
血管通透性增加是蛛网膜下腔出血（SAH）后早期脑损伤的主要原因。但其作用机制尚不清楚。本研究旨在探讨血栓调节蛋白（TM）在蛛网膜下腔出血（SAH）后维持微血管完整性中的作用。通过血管内穿孔在成年雄性ICR小鼠（28-32 g）中建立SAH模型。SAH后立即股静脉注射TM。测定脑含水量、伊文思蓝含量及神经功能。磁共振成像（MRI）（T2图）也检测到脑水肿。采用siRNA技术、酶联免疫吸附试验（ELISA）、免疫荧光染色和蛋白质印迹等方法，探讨TM治疗的可能机制。同时记录海马微血管中微血栓的数量。TM能显著降低SAH后脑含水量和伊文思蓝含量，减轻SAH后脑水肿和神经功能缺损。TM治疗后血浆活化蛋白C浓度升高。此外，磷酸化p38 MAPK、磷酸化p53、裂解型caspase-3、磷酸化NF-κB（p65）水平显著降低。此外，VE-cadherin和Occludin（血管完整性的标志物）的丢失以及海马中微血栓的数量也减少了。本研究结果提示TM对SAH后微血管的保护作用部分是通过保护内皮连接蛋白，抑制p38 MAPK-p53/NF-κB（p65）通路抑制内皮细胞凋亡/炎症反应。
The enhanced vascular permeability is a major early brain injury following subarachnoid hemorrhage (SAH). However, its mechanism is not clear yet. In this work, we explored its potential mechanism and investigated the roles of thrombomodulin (TM) in maintaining microvascular integrity after SAH. SAH models were established in adult male ICR mice (28–32 g) by endovascular perforation. TM was immediately administered by femoral vein injection following SAH. The brain water content, Evans Blue content and neurological functions were evaluated. Brain edema was also detected by magnetic resonance imaging (MRI) (T2 map). The siRNA technique, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and western blotting were performed to explore the potential mechanism of TM treatment. The number of microthrombi in the hippocampus microvessels was also recorded. TM significantly decreased brain water content and Evans Blue content, alleviated brain edema and neurological deficits after SAH. The plasma concentration of activated protein C was increased after TM treatment. In addition, the levels of phospho-p38MAPK, phospho-p53, cleaved caspase-3, phospho-NF-κB (p65) were markedly decreased. Additionally, the loss of VE-cadherin and Occludin (markers of vascular integrity) and the number of microthrombi in the hippocampus were also reduced. Our results indicated that TM has protective effects on preserving microvascular integrity following SAH partly through preserving endothelial junction proteins and quenching apoptosis/inflammation in endothelial cells via blocking p38MAPK-p53/NF-κB (p65) pathway.
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影响因子：
8.3
作者：
Nagai M;Terao S;Yilmaz G;Yilmaz CE;Esmon CT;Watanabe E;Granger DN
通讯作者：
Granger DN
影响因子：
2.9
作者：
DAVIE, EW;FUJIKAWA, K;KISIEL, W
通讯作者：
KISIEL, W
影响因子：
8.3
作者：
Yan J;Manaenko A;Chen S;Klebe D;Ma Q;Caner B;Fujii M;Zhou C;Zhang JH
通讯作者：
Zhang JH
影响因子：
8.3
作者：
GARCIA, JH;WAGNER, S;HU, XJ
通讯作者：
HU, XJ
影响因子：
--
作者：
Nina, P;Schisano, G;Demurtas, F
通讯作者：
Demurtas, F