ADMINISTRATION OF SONIC HEDGEHOG PROTEIN INDUCES ANGIOGENESIS AND HAS THERAPEUTIC EFFECTS AFTER STROKE IN RATS
ADMINISTRATION OF SONIC HEDGEHOG PROTEIN INDUCES ANGIOGENESIS AND HAS THERAPEUTIC EFFECTS AFTER STROKE IN RATS
复制标题
给予 Sonic Hedgehog 蛋白可诱导血管生成并对大鼠中风后具有治疗作用
DOI：
10.1016/j.neuroscience.2017.03.054
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发表时间：
2017-06-03
期刊：
影响因子：
3.3
通讯作者：
Hu, Bo
中科院分区：
文献类型：
--
作者：
Chen, Sheng-Cai;Huang, Ming;Hu, Bo
Sonic hedgehog(Shh)信号通路是对缺血损伤的反应。在这里，我们研究Shh蛋白在缺血性卒中中的临床意义，并探讨其潜在的机制。永久性大脑中动脉闭塞(PMCAO)后即刻侧脑室注射Shh、环多巴胺或抗血管内皮生长因子(VEGF)，持续7d。以磷酸盐缓冲液(PBS)作对照。于pMCAO后7d检测神经功能评分和脑梗塞体积。用异硫氰酸荧光素(FITC)染色和CD31、Ki-67双重染色检测微血管密度，观察体外培养的大鼠脑微血管内皮细胞(RBMECs)在缺氧缺糖(OGD)条件下孵育6h后，加入Shh/抗血管内皮生长因子(Sh/anti-VEGF)，观察血管生成情况。结果发现：(1)Shh可改善神经功能评分，缩小脑梗塞体积，这一作用可被环丙胺阻断；(2)Shh可增加缺血边界区微血管密度，促进血管生成和神经元存活；(3)Shh可增强血管生成，其抗体可逆转Shh的体内、外血管生成和保护作用。这些数据表明，给予Shh蛋白可以保护大脑免受缺血损伤，部分是通过促进血管生成修复。(C)2017年IBRO。爱思唯尔有限公司出版。保留所有权利。
The Sonic hedgehog (Shh) signaling pathway is recapitulated in response to ischemic injury. Here, we investigated the clinical implications of Shh protein in the ischemic stroke and explored the underlying mechanism. lntracerebroventricular injection of Shh, Cyclopamine, or anti-vascular endothelial growth factor (VEGF) was performed immediately after permanent middle cerebral artery occlusion (pMCAO) surgery and lasted for 7 days (d). Phosphate-bufferedi saline (PBS) was used as control. Neurological deficits and infarct volume were examined 7 d after pMCAO. Microvascular density with fluorescein-iso-thio-cyanate (FITC) assay and double staining with CD31 and Ki-67 was measured at 7 d. To observe in vitro angiogenesis, rat brain microvascular endothelial cells (RBMECs) were incubated under oxygen glucose deprivation (OGD) for 6 h (h) and treated with Shh/anti-VEGF. We found that (1) Shh improved neurological scores and reduced infarct volume, which was blocked by Cyclopamine, (2) Shh improved the microvascular density and promoted angiogenesis and neuron survival in the ischemic boundary zone, (3) Shh enhanced VEGF expression and VEGF antibody could reverse angiogenic and protective effect of Shh in vivo and in vitro. These data demonstrate that the administration of Shh protein could protect brain from ischemic injury, in part by promoting angiogenic repair. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.