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Study on the mechanisms responsible for the development and growth of dural arteriovenous fistula

硬脑膜动静脉瘘发生和生长的机制研究

基本信息

批准号：
14370444
负责人：
SAKAKI Toshisuke
金额：
$ 6.72万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Although various mechanisms of the development of dural arteriovenous fistula(DAVF) have been proposed, the pathogenesis of these lesions are still unclear. Recent experimental evidence suggested a role of angiogenic growth factors in the genesis of vascular malformations of the central nervous system. To further investigate the pathogenesis of DAVF, we examined the expression of the angiogenic growth factor, vascular endothelial growth factor(VEGF), in rat DAVF model.<Experiment-1> Male Wistar rats were used. DAVF model (Spetzler) was made, and venous hypertension was induced which were divided into two experimental groups ; immunohistological study group and angiography group. Immunohistological analysis was performed by VEGF antibody 1 week after, and angiography was done 90 days after the surgery. As a result, VEGF expression in the endothelium and the connective tissues of the dura matter in the five rats (33%) and in the neurons in the eleven rats (73%) of the cerebral cortex and the basal ganglia were identified. DAVF formed in 6 among 15 rats (40%). <Experiment-2> Western blot was performed with different periods from 1, 2 and 3 weeks after inducing venous hypertension in the same model. The expression of VEGF was peaked at one week after venous hypertension, and decreased by the order of two and three weeks (1>2>3 week). The expression of immunoreactive VEGF was restricted in the connective tissue and the endothelial layer of the dura matter, cerebral cortical tissue and basal ganglia neurons.In conclusions, these results strongly suggest a possible contribution of the VEGF system to the growth of DAVF. Venous ischemia by venous hypertension might be responsible for inducing up-regulation of angiogenic factor expression.

虽然硬脑膜动静脉瘘（DAVF）的发生机制多种多样，但其发病机制仍不清楚。最近的实验证据表明，血管生成生长因子在中枢神经系统血管畸形的发生中的作用。为了进一步研究DAVF的发病机制，我们检测了大鼠DAVF模型中血管生成生长因子血管内皮生长因子（VEGF）的表达。<Experiment-1>使用雄性Wistar大鼠。制作DAVF模型（Spetzler法），建立静脉高压模型，分为两个实验组：免疫组化组和血管造影组。术后1周行VEGF抗体免疫组化染色，术后90天行血管造影。结果，在5只大鼠（33%）的硬脑膜的内皮和结缔组织中以及在11只大鼠（73%）的大脑皮层和基底神经节的神经元中鉴定出VEGF表达。15只大鼠中有6只（40%）形成DAVF。<Experiment-2>在同一动物模型上，分别于诱导静脉高压后1、2、3周进行Western blot检测。VEGF表达在静脉高压后1周达高峰，2、3周依次下降（1>2>3周）。免疫反应阳性的VEGF表达仅限于硬脑膜的结缔组织和内皮层、大脑皮质组织和基底节神经元。静脉高压引起的静脉缺血可能是导致血管生成因子表达上调的原因。