Increased Expression of Vascular Endothelial Growth Factor Protein in Dorsal Root Ganglion Exposed to Nucleus Pulposus on the Nerve Root in Rats
Increased Expression of Vascular Endothelial Growth Factor Protein in Dorsal Root Ganglion Exposed to Nucleus Pulposus on the Nerve Root in Rats
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DOI：
10.1097/brs.0b013e3181d345fa
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发表时间：
2011-01-01
期刊：
影响因子：
3
通讯作者：
Kanaya, Fuminori
中科院分区：
文献类型：
--
作者：
Miyoshi, Shinji;Sekiguchi, Miho;Kanaya, Fuminori
研究设计.一项大鼠实验研究。目的：研究髓核（NP）对大鼠神经根疼痛行为和血管内皮生长因子（VEGF）表达的影响。椎间盘突出引起的神经根病是由神经压迫和化学炎症引起的。在实验研究中，当NP应用于神经根时，报告了机械撤回阈值、血流量和神经根功能障碍的降低。然而，神经元的再生和神经根血管的变化还没有得到明确的理解。从尾部收获的NP应用于左侧L5背根神经节（NP组; n = 77）。作为对照，使用假手术动物（n = 77）。用von Frey毛发进行35天的行为测试。通过免疫组织化学研究VEGF、转录激活因子-3、生长相关蛋白-43（GAP-43）、因子VIII和缺氧诱导因子-1 α（HIF-1 α）的免疫反应性（IR）。还对VEGF和GAP-43进行了蛋白质印迹分析。结果。与假手术组相比，NP组7 ~ 28天机械性缩足阈显著降低（P < 0.05）。与假手术组相比，NP组中活化转录因子-3-IR细胞从3天到14天增加（P < 0.05），缺氧诱导因子-1 α-IR细胞在14天增加（P < 0.05），具有因子VII-IR细胞的血管在28天增加（P < 0.05）。NP组VEGF和GAP-43的表达水平在14、28 d时明显升高（P <0. 05）。NP作用于神经根早期引起神经元损伤，14 d开始出现轴突延伸。VEGF在术后14和28天增加，血管数量在术后28天增加。在35天时，机械撤回阈值有所改善。血管内皮生长因子的再生和血管化可能与疼痛相关的行为。
Study Design. An experimental rat study.Objective. To assess pain-related behavior and vascular endothelial growth factor (VEGF) expression induced by nucleus pulposus (NP) applied to nerve roots in rats.Summary of Background Data. Radiculopathy from disc herniation is caused by nerve compression and chemical inflammation. In experimental studies, a decrease in mechanical withdrawal threshold, blood flow, and nerve root dysfunction was reported when the NP was applied to nerve roots. However, neuron reproduction and changes in nerve root blood vessels have not been clearly understood.Methods. NP harvested from the tail was applied to the left L5 dorsal root ganglion (NP group; n = 77). As a control, sham-operated animals were used (n = 77). Behavioral testing with von Frey hairs was performed for 35 days. Immunoreactivity (IR) for VEGF, activating transcription factor-3, growth-associated protein-43 (GAP-43), factor VIII, and hypoxia-inducible factor-1 alpha (HIF-1 alpha) were studied by immunohistochemistry. Western blot analyses of VEGF and GAP-43 were also performed.Results. The mechanical withdrawal threshold significantly decreased from 7 to 28 days in the NP group versus the sham group (P < 0.05). In the NP group, activating transcription factor-3-IR cells increased from 3 to 14 days (P < 0.05), hypoxia-inducible factor-1 alpha-IR cells increased at 14 days (P < 0.05), and blood vessels with Factor VII-IR cells increased at 28 days (P < 0.05) compared with the sham group. The expression levels of VEGF and GAP-43 in the NP group significantly increased at 14 and 28 days (P < 0.05).Conclusion. Neuron damage induced by NP applied to the nerve root at the early stage, and axon extension occurred from 14 days. VEGF increased at 14 and 28 days, and the numbers of blood vessels increased 28 days after surgery. The mechanical withdrawal threshold improved at 35 days. Regeneration and vascularization by VEGF might be associated with pain-related behavior.