Bay11-7082 attenuates neuropathic pain via inhibition of nuclear factor-kappa B and nucleotide-binding domain-like receptor protein 3 inflammasome activation in dorsal root ganglions in a rat model of lumbar disc herniation.
Bay11-7082 attenuates neuropathic pain via inhibition of nuclear factor-kappa B and nucleotide-binding domain-like receptor protein 3 inflammasome activation in dorsal root ganglions in a rat model of lumbar disc herniation.
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Bay11-7082 通过抑制腰椎间盘突出大鼠模型背根神经节中的核因子 kappa B 和核苷酸结合域样受体蛋白 3 炎症小体激活来减轻神经性疼痛
DOI：
10.2147/jpr.s119820
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发表时间：
2017
影响因子：
2.7
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Zhang A;Wang K;Ding L;Bao X;Wang X;Qiu X;Liu J
腰椎间盘突出症（LDH）是神经根病的一个重要原因，但其潜在机制尚不完全清楚。许多研究表明，局部炎症，而不是机械压迫，导致LDH诱导的神经根病。核因子-κ B（NF-κB）和核苷酸结合域样受体蛋白3（NLRP 3）炎性体在分子和细胞水平上参与了神经炎症的形成和发展。本研究将自体髓核（NP）植入大鼠左侧L5背根神经节（DRG），模拟LDH。本实验观察了NF-κB B和NLRP 3炎性体成分在大鼠DRG神经元中的表达。采用免疫印迹法和免疫荧光法检测NLRP 3、caspase-1激活域相关斑点样蛋白（ASC）、caspase-1、白细胞介素（IL）-1β、IL-18、IκBα、p-IκB α、p65、p-p65和降钙素基因相关肽（CGRP）。NP治疗组大鼠DRG神经元NLRP 3、ASC、caspase-1、IL-1β、IL-18、p-IκBα和p-p65的活化在术后1 d即升高，并在术后7 d达到高峰。用IKK-β作用抑制剂Bay 11 -7082治疗能够抑制分子（NLRP 3、ASC、caspase-1、IL-1β、IL-18、p-IκBα和p-p65）的表达和活化，并减轻大鼠的疼痛。我们的研究表明NF-κB和NLRP 3炎性体参与了NP引起的疼痛的维持，Bay 11 -7082可以通过抑制NF-κB和NLRP 3炎性体的激活来减轻机械性痛觉超敏和热痛觉过敏。
Lumbar disc herniation (LDH) is an important cause of radiculopathy, but the underlying mechanisms are incompletely understood. Many studies suggested that local inflammation, rather than mechanical compression, results in radiculopathy induced by LDH. On the molecular and cellular level, nuclear factor-kappa B (NF-κB) and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome have been implicated in the regulation of neuroinflammation formation and progression. In this study, the autologous nucleus pulposus (NP) was implanted in the left L5 dorsal root ganglion (DRG) to mimic LDH in rats. We investigated the expression of NF-κB and the components of NLRP3 inflammasome in the DRG neurons in rats. Western blotting and immunofluorescence for the related molecules, including NLRP3, apoptosis-associated speck-like protein containing caspase-1 activator domain (ASC), caspase-1, interleukin (IL)-1β, IL-18, IκBα, p-IκBα, p65, p-p65, and calcitonin gene-related peptide (CGRP) were examined. In the NP-treated group, the activations of NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 in DRG neurons in rats were elevated at 1 day after surgery, and the peak occurred at 7 days. Treatment with Bay11-7082, an inhibitor of the actions of IKK-β, was able to inhibit expression and activation of the molecules (NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65) and relieve the pain in rats. Our study shows that NF-κB and NLRP3 inflammasome are involved in the maintenance of NP-induced pain, and that Bay11-7082 could alleviate mechanical allodynia and thermal hyperalgesia by inhibiting NF-κB and NLRP3 inflammasome activation.