中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (10): 1726-1733.doi: 10.4103/1673-5374.257530

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

血管内皮生长因子A大量表达可促进血小板黏附IV型胶原，并引发蛛网膜下腔出血后早期脑损伤

  

  • 出版日期:2019-10-15 发布日期:2019-10-15
  • 基金资助:

    中国国家自然科学基金项目（81471179）

Vascular endothelial growth factor A promotes platelet adhesion to collagen IV and causes early brain injury after subarachnoid hemorrhage

Zun-Wei Liu 1, 2, Jun-Jie Zhao 3, Hong-Gang Pang 4, Jin-Ning Song 3   

  1. 1 Department of Renal Transplantation, Nephropathy Hospital, the First Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
    2 Institute of Organ Transplantation, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
    3 Department of Neurosurgery, the First Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
    4 The First Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
     
  • Online:2019-10-15 Published:2019-10-15
  • Contact: Jin-Ning Song, MD, jinningsong@126.com
  • Supported by:

    This study was financially supported by the National Natural Science Foundation of China, No. 81471179 (to JNS).

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摘要：

动脉瘤性蛛网膜下腔出血后发生血小板粘连及其在早期脑损伤中的作用目前还不清楚。因此实验拟以颅内颈内动脉闭塞30s建立蛛网膜下腔出血模型，30min后于右侧脑室内注射抗血管内皮生长因子受体2抗体10μg。(1)以免疫组织化学检测海马组织中血管内皮生长因子A，Occludin和Claudin-5的免疫阳性反应，以Western blot检测海马组织中血管内皮生长因子A，Occludin以及Claudin-5的表达，以双标免疫组化染色检测海马组织中与血小板黏附有关的GP Ia-II整联蛋白与IV型胶原共表达情况，以TUNEL检测海马组织中细胞凋亡情况，以神经功能缺陷评分评价大鼠的运动能力。(2)结果显示，蛛网膜下腔出血后，大鼠海马组织中血管内皮生长因子A表达水平以及免疫阳性反应增加，Occludin和Claudin-5表达水平以及免疫阳性反应减少； GP Ia-II整联蛋白与IV型胶原共表达以及TUNEL阳性细胞数量增加，大鼠运动能力明显损伤；使用抗血管内皮生长因子受体2抗体干预后Occludin和Claudin-5表达水平以及免疫阳性反应恢复。GP Ia-II整联蛋白与IV型胶原共表达以及TUNEL阳性细胞数量明显减少，运动能力显著恢复；(3)实验结果说明，大量表达的血管内皮生长因子A可能导致血小板黏附并刺激蛛网膜下腔出血后早期脑损伤的发生。实验于2015年12月经西安交通大学医学院生物医学伦理委员会批准，批准号SYXK [Shaan] 2015-002。

orcid: 0000-0002-0620-8983 (Jin-Ning Song)

关键词: 血管内皮生长因子A, 血管内皮生长因子受体2, 蛛网膜下腔出血, 脑损伤, 血小板黏附, 胶原, 血脑屏障, 神经再生

Abstract:

The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear. In this study, the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage. Then, 30 minutes later, vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody, 10 μg, was in¬jected into the right ventricle. Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A, occludin and claudin-5. Immunohistochemical double labeling was conducted to examine co-expression of GP Ia-II integrin and type IV collagen. TUNEL was used to detect apoptosis in the hippocampus. Neurological score was used to assess behavioral performance. After subarachnoid hemorrhage, the expression of vascular endothelial growth factor A increased in the hippocampus, while occludin and claudin-5 expression levels decreased. Co-expression of GP Ia-II integrin and type IV collagen and the number of apoptotic cells increased, whereas behavioral performance was markedly impaired. After treatment with anti-vascular endothelial growth factor receptor 2 antibody, occludin and claudin-5 expression recovered, while co-expression of GP Ia-II integrin and type IV collagen and the number of apoptotic cells decreased. Furthermore, behavioral performance improved notably. Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage. This study was approved by the Biomedical Ethics Committee, Medical College of Xi’an Jiaotong University, China in December 2015 (SYXK [Shaan] 2015-002).

Key words: nerve regeneration, vascular endothelial growth factor A, vascular endothelial growth factor receptor 2, subarachnoid hemorrhage, brain injuries, platelet adhesion, collagen, blood-brain barrier, neural regeneration