Epoxyeicosanoids prevent intervertebral disc degeneration in vitro and in vivo.
Epoxyeicosanoids prevent intervertebral disc degeneration in vitro and in vivo.
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环氧类二十烷酸可在体外和体内预防椎间盘退变。
DOI：
10.18632/oncotarget.14389
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发表时间：
2017-01-17
期刊：
影响因子：
--
通讯作者：
Li F
中科院分区：
文献类型：
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作者：
Li J;Guan H;Liu H;Zhao L;Li L;Zhang Y;Tan P;Mi B;Li F
椎间盘退变被认为是腰痛的常见原因。在退变的椎间盘中，包括白细胞介素 - 1（IL - 1）和肿瘤坏死因子 - α（TNF - α）在内的促炎细胞因子的产生逐渐增加，从而促进了退变过程。环氧二十碳三烯酸（EETs）是由细胞色素P450酶从花生四烯酸合成的，在调节炎症、心血管功能和血管生成方面作为自分泌和旁分泌效应物发挥作用。EETs已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是否能够影响椎间盘退变。我们发现14,15 - EET在体外可保护大鼠髓核（NP）细胞免受过氧化氢（H₂O₂）和TNF - α处理诱导的死亡。在分子水平上，14,15 - EET显著抑制了核因子 - κB（NF - κB）通路，该通路在NP细胞的退变和存活中起着关键作用。因此，14,15 - EET有效地阻止了NP细胞对TNF - α的基质重塑反应。利用针刺大鼠尾模型，通过X线片、磁共振成像（MRI）和组织学分析评估了14,15 - EET在体内对椎间盘退变的影响。我们观察到14,15 - EET可防止椎间盘退变。我们的研究结果表明，14,15 - EET能够提高NP细胞的存活率并抑制椎间盘退变。EET通路可能是治疗椎间盘退变的一个新的治疗靶点。
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.