Induction of interleukin-6 in dorsal root ganglion neurons after gradual elongation of rat sciatic nerve
Induction of interleukin-6 in dorsal root ganglion neurons after gradual elongation of rat sciatic nerve
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DOI：
10.1016/j.expneurol.2005.03.019
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发表时间：
2005-09-01
影响因子：
5.3
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
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作者：
Osamura, N;Ikeda, K;Yokoyama, S
在周围神经节段性缺损的修复中，逐渐延长神经已成为神经移植的重要替代方法。为了阐明神经延长后外周感觉神经元的生化反应，我们检测了与神经再生相关的细胞因子和神经营养因子的表达。我们首先建立了大鼠股骨延长模型，以1.0、2.0或20.0 mm/天的速度延长左侧股骨至20.0 mm。在甲苯胺蓝染色，急性拉长，20毫米/天组显示核偏心的神经细胞体在L5背根神经节（DRG）和轴突变性的坐骨神经;相反，逐渐拉长，1和2毫米/天组保持完整，表明适应。逆转录-聚合酶链反应分析显示，白细胞介素-6（IL-6）mRNA在同侧L4-6 DRG中以延长率依赖的方式被诱导。相比之下，细长组中的白细胞介素-1 β、肿瘤坏死因子-a、神经生长因子、脑源性神经营养因子、神经营养素-3和神经营养素-4/5的mRNA水平均未出现显着变化。IL-6 mRNA的水平在所有延长组达到最高水平后，在第4天延长20毫米，而轴突切断组显示从第1天的最高水平下降。在所有延长组的对侧L4-6 DRG中也检测到IL-6 mRNA的诱导，但在轴突切断组中未检测到。在组织化学分析中，IL-6免疫反应主要是在neuroendocrine阳性，中型至大型DRG神经元。应用IL-6培养的雪旺细胞增加外周髓鞘蛋白22（PMP 22），一个主要的髓鞘成分的mRNA。这些结果表明，IL-6在逐渐延长的神经后外周感觉神经元的生化反应中起着关键作用。(c)2005年爱思唯尔公司All rights reserved.
In the reconstruction of a segmental defect in injured peripheral nerves, gradual nerve elongation has become an important alternative to nerve grafting. To clarify biochemical responses in peripheral sensory neurons after nerve elongation, we examined the expression of cytokines and neurotrophins related to nerve regeneration. We first established rat elongation models by lengthening left femurs up to 20.0 mm at the rate of 1.0, 2.0, or 20.0 mm/day. In toluidine blue staining, the acutely elongated, 20-mm/day group showed nuclear eccentricity in the nerve cell body in L5 dorsal root ganglion (DRG) and axonal degeneration in the sciatic nerves; in contrast, the gradually elongated, 1-and 2-mm/day groups remained intact, indicating adaptation. Reverse transcription-polymerase chain reaction analysis revealed that interleukin-6 (IL-6) mRNA was induced in ipsilateral L4-6 DRG in an elongation rate-dependent manner. In contrast, none of the elongated groups exhibited a significant change in mRNA levels for interleukin-1 beta, tumor necrosis factor-a, nerve growth factor, brain-derived neurotrophic factor, neurotropnin-3, and neurotrophin-4/5. Levels of IL-6 mRNA in all the elongated groups reached the maximum level at day 4 after 20-mm lengthening, while the axotomized group showed a decrease from the maximum level at day 1. Induction of IL-6 mRNA was also detected in the contralateral L4-6 DRG of all the elongated groups, but not detected in the axotomized group. In histochemical analysis, IL-6-immunoreactivity was predominant in neurofilament-positive, medium to large DRG neurons. Application of IL-6 to cultured Schwann cells increased mRNA for peripheral myelin protein 22 (PMP22), a major myelin component. These results suggest that IL-6 plays a key role in biochemical responses in peripheral sensory neurons after gradual nerve elongation. (c) 2005 Elsevier Inc. All rights reserved.