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

尽管已经提出了硬脑膜动静脉瘘（DAVF）发生的各种机制，但这些病变的发病机制仍不清楚。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发生中的作用。为了进一步探讨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。<实验-1>选用雄性Wistar大鼠。造DAVF模型（Spetzler），诱导静脉高压症，分为2个实验组；免疫组织学研究组和血管造影组。术后1周行VEGF抗体免疫组织学分析，术后90天行血管造影。结果，在5只大鼠（33%）的硬脑膜内皮和结缔组织以及11只大鼠（73%）的大脑皮层和基底节区神经元中检测到VEGF的表达。15只大鼠中有6只形成DAVF（40%）。<实验-2> >在同一模型诱导静脉高压后1、2、3周不同时期进行Western blot。血管内皮生长因子的表达在静脉高压后1周达到高峰，随后依次下降（1周、2周、3周）。免疫反应性VEGF在结缔组织、硬脑膜内皮层、大脑皮质组织和基底神经节神经元中表达受限。总之，这些结果强烈提示VEGF系统可能对DAVF的生长有贡献。静脉高压引起的静脉缺血可能是引起血管生成因子表达上调的原因。

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.