Li Jing, Guan Hanfeng, Liu Huiyong, Zhao Libo, Li Li, Zhang Yong, Tan Peng, Mi Baoguo, Li Feng
Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Oncotarget. 2017 Jan 17;8(3):3781-3797. doi: 10.18632/oncotarget.14389.
Intervertebral disc (IVD) degeneration is considered a common cause of low back pain. In the degenerating IVD, the production of pro-inflammatory cytokines, including IL-1 and TNF-α, progressively increases, contributing to the degenerative process. Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 enzymes, act as autocrine and paracrine effectors in regulating inflammation, cardiovascular functions, and angiogenesis. EETs were shown to be especially potent promoters of tissue regeneration. Considering their anti-inflammatory and anti-catabolic potential, we investigated whether EETs can influence IVD degeneration. We found that 14,15-EET protected rat nucleus pulposus (NP) cells against death induced by treatment with H2O2and TNF-α in vitro. At the molecular level, 14,15-EET significantly inhibited the NF-κB pathway, which plays essential roles in the degeneration and survival of NP cells. As a result, 14,15-EET efficiently prevented the matrix remodeling response of NP cells to TNF-α. Using a needle-punctured rat tail model, the influence of 14,15-EET on IVD degeneration in vivo was evaluated using radiographs, magnetic resonance images (MRI), and histological analysis. We observed that 14,15-EET prevented IVD degeneration. Our findings demonstrated that 14,15-EET can enhance the survival of NP cells and inhibit IVD degeneration. The EET pathway may be a novel therapeutic target against IVD degeneration.
椎间盘（IVD）退变被认为是下腰痛的常见原因。在退变的IVD中，包括白细胞介素-1和肿瘤坏死因子-α在内的促炎细胞因子的产生逐渐增加，促进了退变过程。环氧二十碳三烯酸（EETs）由细胞色素P450酶从花生四烯酸合成，在调节炎症、心血管功能和血管生成中作为自分泌和旁分泌效应物发挥作用。EETs被证明是组织再生的特别有效的促进剂。考虑到它们的抗炎和抗分解代谢潜力，我们研究了EETs是否能影响IVD退变。我们发现14,15-EET在体外保护大鼠髓核（NP）细胞免受过氧化氢和肿瘤坏死因子-α处理诱导的死亡。在分子水平上，14,15-EET显著抑制NF-κB通路，该通路在NP细胞的退变和存活中起重要作用。因此，14,15-EET有效地阻止了NP细胞对肿瘤坏死因子-α的基质重塑反应。使用针刺大鼠尾部模型，通过X线片、磁共振成像（MRI）和组织学分析评估14,15-EET对体内IVD退变的影响。我们观察到14,15-EET可预防IVD退变。我们的研究结果表明，14,15-EET可提高NP细胞的存活率并抑制IVD退变。EET通路可能是对抗IVD退变的新治疗靶点。
