A Novel Mechanism of Specialized Proresolving Lipid Mediators Mitigating Radicular Pain: The Negative Interaction with NLRP3 Inflammasome
A Novel Mechanism of Specialized Proresolving Lipid Mediators Mitigating Radicular Pain: The Negative Interaction with NLRP3 Inflammasome
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专门解决脂质介质减轻根性疼痛的新机制：与 NLRP3 炎性体的负面相互作用
DOI：
10.1007/s11064-020-03050-x
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发表时间：
2020-05
影响因子：
4.4
通讯作者：
Tao Sun
中科院分区：
文献类型：
--
作者：
Yi-Hao Wang;Yan Li;Jun-Nan Wang;Qing-Xiang Zhao;Shuang Wen;Si-Cong Wang;Tao Sun
抑制髓核暴露引起的免疫和炎症反应可有效改善腰椎间盘突出症的神经性疼痛。作为巨噬细胞来源的炎症消退介质，Maresin1 （MaR1）显示出强大的抗炎作用。在本研究中，我们试图阐明MaR1对神经根性疼痛的影响及其与NLRP3炎性体的相互作用。建立非压缩性腰椎间盘突出症大鼠模型，给予不同剂量（MaR1或Caspase-1抑制剂）。观察足退缩潜伏期（PWL）和足退缩阈值（PWTs）来评估疼痛行为。采集脊髓角，采用ELISA法检测IL-1β和IL-18水平。采用RT-PCR、western blot和免疫组织化学检测NLRP3炎性小体组分mRNA和蛋白表达水平。采用LC-MS /MS分析脊髓内源性MaR1水平。NP在模型中的应用导致机械和热过敏，IL-1β和IL-18水平升高以及NLRP3炎症小体成分的表达，而给药MaR1可显著逆转这一现象。Caspase-1抑制还能改善机械超敏反应，降低炎症细胞因子的表达，抑制炎症小体的活化。同时，Caspase-1抑制剂促进内源性MaR1的合成，这在疼痛模型中受到阻碍。综上所述，我们的研究表明，MaR1和NLRP3炎症小体之间的负相互作用介导了脊髓背角的炎症反应，参与了神经根痛的发病机制。
Inhibition of immune and inflammatory reaction induced by the expose of nucleus pulposus (NP) could effectively ameliorate neuropathic pain in the lumbar disc herniation. Maresin1 (MaR1), as a macrophage-derived mediator of inflammation resolution, displayed potent anti-inflammatory action. In the present study, we attempted to elucidate the impact of MaR1 on radicular pain and the interaction with NLRP3 inflammasome. We established a rat model of non-compressive lumbar disc herniation and different administration (MaR1 or Caspase-1 inhibitor) was given to them. The paw withdrawal latency (PWL) and paw withdrawal thresholds (PWTs) were observed to assess pain behaviors. The spinal cord horns were collected and the levels of IL-1β and IL-18 were measured by ELISA. The mRNA and protein expression levels of NLRP3 inflammasome components were tested by RT-PCR, western blot and immunohistochemistry. The endogenous MaR1 levels of the spinal cord were analyzed using LC–MS/MS. The application of NP in the models lead to mechanical and thermal hypersensitivity, increased IL-1β and IL-18 levels and expressions of NLRP3 inflammasome components, which were reversed markedly by administration of MaR1. Caspase-1 inhibition also improved mechanical hypersensitivity, decreased the expressions of inflammatory cytokines and restrained the activation of inflammasome. Meanwhile, Caspase-1 inhibitor promoted the endogenous MaR1 synthesis, which was hindered in the pain models. Altogether, our study indicated that the negative interaction between MaR1 and NLRP3 inflammasome mediated the inflammatory response in spinal dorsal horn, which involved in the pathogenesis of radicular pain.
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影响因子：
5.3
作者：
Tonkin, Ryan S.;Bowles, Callum;Moalem-Taylor, Gila
通讯作者：
Moalem-Taylor, Gila
DOI：
10.1016/j.bbalip.2014.08.006
发表时间：
2015-04
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Serhan CN;Dalli J;Colas RA;Winkler JW;Chiang N
通讯作者：
Chiang N
Omega-3 脂肪酸通过抑制 NLRP3 炎症小体激活来预防炎症和代谢紊乱。
影响因子：
32.4
作者：
Yan, Yiqing;Jiang, Wei;Zhou, Rongbin
通讯作者：
Zhou, Rongbin
影响因子：
8.8
作者：
Liu, Zhi-hua;Miao, Gui-shen;Sun, Tao
通讯作者：
Sun, Tao
在非压迫性腰椎间盘突出症大鼠模型中，脂氧素 A4 可能通过抑制脊髓 ERK、JNK 和 NF-κB/p65 和细胞因子信号（但不是 p38）来减轻神经根痛
影响因子：
3.3
作者：
Miao, G. -S;Liu, Z. -H;Sun, T.
通讯作者：
Sun, T.