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在大鼠神经根受压的背根神经节中血管内皮生长因子蛋白表达增加。

Increased expression of vascular endothelial growth factor protein in dorsal root ganglion exposed to nucleus pulposus on the nerve root in rats.

机构信息

Department of Orthopedic Surgery, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.

出版信息

Spine (Phila Pa 1976). 2011 Jan 1;36(1):E1-6.

Abstract

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 a) 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.

摘要

研究设计

一项实验性大鼠研究。

目的

评估椎间盘突出物(NP)施加于大鼠神经根引起的疼痛相关行为和血管内皮生长因子(VEGF)表达。

背景资料概要

椎间盘突出引起的神经根病变是由神经压迫和化学炎症引起的。在实验研究中,当 NP 施加于神经根时,报道了机械退缩阈值、血流和神经根功能障碍的降低。然而,神经元再生和神经根血管的变化尚不清楚。

方法

从尾巴中提取 NP 并施加于左侧 L5 背根神经节(NP 组;n = 77)。作为对照,使用假手术动物(n = 77)。使用 von Frey 毛发进行 35 天行为测试。通过免疫组织化学研究 VEGF、激活转录因子-3、生长相关蛋白-43(GAP-43)、VIII 因子和缺氧诱导因子-1[alpha](HIF-1 a)的免疫反应性(IR)。还进行了 VEGF 和 GAP-43 的 Western blot 分析。

结果

与假手术组相比,NP 组从第 7 天到第 28 天的机械退缩阈值显著降低(P < 0.05)。在 NP 组中,从第 3 天到第 14 天,激活转录因子-3-IR 细胞增加(P < 0.05),第 14 天缺氧诱导因子-1[alpha]-IR 细胞增加(P < 0.05),第 28 天 VIII 因子阳性血管增加(P < 0.05)。与假手术组相比,NP 组 VEGF 和 GAP-43 的表达水平在第 14 天和第 28 天显著增加(P < 0.05)。

结论

NP 施加于神经根早期引起神经元损伤,从第 14 天开始出现轴突延伸。VEGF 在第 14 天和第 28 天增加,手术后第 28 天血管数量增加。在第 35 天,机械退缩阈值得到改善。VEGF 引起的再生和血管生成可能与疼痛相关行为有关。

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