大鼠实验性椎间盘突出以肿瘤坏死因子依赖的方式导致血清素受体2c下调。
Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner.
作者信息
Jonsson Daniel, Finskas Oscar, Fujioka Yuki, Ståhlberg Anders, Olmarker Kjell
机构信息
Musculoskeletal Research, Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30, Gothenburg, Sweden.
出版信息
Clin Orthop Relat Res. 2015 Jun;473(6):1913-9. doi: 10.1007/s11999-014-3878-1.
BACKGROUND
During recent decades, the knowledge of the pathophysiology of disc herniation and sciatica has drastically improved. What previously was considered a strict biomechanical process is now considered a more complex interaction between leaked nucleus pulposus and the tissue in the spinal canal. An inflammatory reaction, with tumor necrosis factor (TNF) playing an essential role, has been demonstrated. However, the exact mechanisms of the pathophysiology of disc herniation remain unknown.
QUESTIONS/PURPOSES: In this study we use an animal model to investigate (1) if and/or how experimental disc herniation affects gene expression in the early phase (24 hours postsurgery) in the dorsal root ganglion; and (2) if TNF inhibition can reduce any observed changes.
METHODS
A rat model of disc herniation was used. Twenty rats were evenly divided into four groups: naïve, sham, disc herniation, and disc herniation with TNF inhibition. The dorsal root ganglion of the affected nerve root was harvested 24 hours after surgery and analyzed with a TaqMan Low Density Array(®) quantitative polymerase chain reaction assay. Gene expression levels in sham were compared with disc herniation to assess question 1 and disc herniation to disc herniation with TNF inhibition to assess question 2.
RESULTS
Experimental disc herniation caused a decrease in the expression of the serotonin receptor 2c gene (p = 0.022). TNF inhibition was found to reduce the observed decrease in expression of serotonin receptor 2c (p = 0.037).
CONCLUSIONS
Our results suggest that a decrease in the expression of the serotonin receptor 2c gene may contribute to the pathophysiology of disc herniation. Further research on its involvement is warranted.
CLINICAL RELEVANCE
This pilot study gives a brief insight into cellular changes that may contribute to the pathophysiology of disc herniation. This knowledge may contribute to the development of more and better treatment options for patients with disc herniation and sciatica.
背景
在最近几十年里，椎间盘突出症和坐骨神经痛的病理生理学知识有了显著进步。以前被认为是一个严格的生物力学过程，现在则被认为是髓核渗漏与椎管内组织之间更为复杂的相互作用。已经证实，一种以肿瘤坏死因子（TNF）起关键作用的炎症反应存在。然而，椎间盘突出症病理生理学的确切机制仍然未知。
问题/目的：在本研究中，我们使用动物模型来研究：（1）实验性椎间盘突出症是否以及如何影响背根神经节早期（术后24小时）的基因表达；以及（2）TNF抑制是否能减少任何观察到的变化。
方法
采用大鼠椎间盘突出症模型。20只大鼠平均分为四组：未处理组、假手术组、椎间盘突出症组和TNF抑制的椎间盘突出症组。术后24小时采集受影响神经根的背根神经节，并用TaqMan低密度阵列定量聚合酶链反应分析。将假手术组的基因表达水平与椎间盘突出症组比较以评估问题1，将椎间盘突出症组与TNF抑制的椎间盘突出症组比较以评估问题2。
结果
实验性椎间盘突出症导致血清素受体2c基因表达降低（p = 0.022）。发现TNF抑制可减少血清素受体2c表达的观察到的降低（p = 0.037）。
结论
我们的结果表明，血清素受体2c基因表达降低可能促成椎间盘突出症的病理生理学。对其参与情况进行进一步研究是必要的。
临床意义
这项初步研究简要洞察了可能促成椎间盘突出症病理生理学的细胞变化。这一知识可能有助于为椎间盘突出症和坐骨神经痛患者开发更多更好的治疗选择。
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