Dou Limin, Yu Wenhua
Department of Neurosurgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China.
Department of Neurosurgery, The Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Exp Ther Med. 2017 Nov;14(5):5114-5120. doi: 10.3892/etm.2017.5174. Epub 2017 Sep 21.
Intracranial dural arteriovenous fistulas (DAVFs) are complex intracranial vascular malformations that may lead to hemorrhage. Although the precise mechanisms by which DAVFs occur remain unknown, dural angiogenesis may be a vital factor in its pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) significantly influences angiogenesis; however, the association between DAVF and Nrf2 remains unclear. Therefore, the present study investigated whether DAVF alters the expression of Nrf2 in an experimental animal model of DAVF. The DAVF group underwent surgery of the left common carotid artery-external jugular vein anastomosis, cauterization of the vein draining transverse sinus and thrombosis of the sagittal sinus to induce venous hypertension (VH). At 1, 4 and 7 days post surgery, rats were sacrificed to collect brain samples. Western blot analysis, immunofluorescence staining and reverse transcription-quantitative polymerase chain reaction were used to determine whether DAVF activated the Nrf2 signaling pathway. The results demonstrated that the expression of Nrf2 mRNA and protein, and the expression of its downstream genes heme oxygenase-1 and NAD(P)H: quinine oxidoreductase-1 significantly increased 1 day after surgery. The expression of these genes decreased but remained high 4 days following surgery and only returned to baseline 7 days after surgery. Compared with the sham-surgery and control groups, DAVF-induced brain edema reached a peak 1 day following DAVF surgery and only returned to normal levels 7 days post-surgery. Taken together, these data indicate the potential contribution of Nrf2 to the formation of DAVFs and suggest that VH may induce the upregulation of Nrf2.
颅内硬脑膜动静脉瘘（DAVF）是一种复杂的颅内血管畸形，可能导致出血。尽管DAVF发生的确切机制尚不清楚，但硬脑膜血管生成可能是其发病机制中的一个重要因素。核因子红细胞2相关因子2（Nrf2）对血管生成有显著影响；然而，DAVF与Nrf2之间的关联仍不清楚。因此，本研究在DAVF实验动物模型中研究了DAVF是否会改变Nrf2的表达。DAVF组进行了左颈总动脉-颈外静脉吻合术、横窦引流静脉烧灼术和矢状窦血栓形成术以诱导静脉高压（VH）。术后1、4和7天，处死大鼠以收集脑样本。采用蛋白质免疫印迹分析、免疫荧光染色和逆转录定量聚合酶链反应来确定DAVF是否激活了Nrf2信号通路。结果表明，术后1天，Nrf2 mRNA和蛋白的表达及其下游基因血红素加氧酶-1和NAD（P）H：醌氧化还原酶-1的表达显著增加。这些基因的表达在术后4天下降但仍保持较高水平，仅在术后7天恢复到基线水平。与假手术组和对照组相比，DAVF诱导的脑水肿在DAVF手术后1天达到峰值，仅在术后7天恢复到正常水平。综上所述，这些数据表明Nrf2对DAVF形成的潜在作用，并提示VH可能诱导Nrf2上调。
