Glucocorticoid receptor inhibit the activity of NF-kappa B through p38 signaling pathway in spinal cord in the spared nerve injury rats
Glucocorticoid receptor inhibit the activity of NF-kappa B through p38 signaling pathway in spinal cord in the spared nerve injury rats
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糖皮质激素受体通过p38信号通路抑制神经损伤大鼠脊髓NF-κB活性
DOI：
10.1016/j.lfs.2018.07.026
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发表时间：
2018
期刊：
影响因子：
6.1
通讯作者：
Zang Weidong
中科院分区：
文献类型：
--
作者：
Shao Jinping;Xu Ruiyan;Li Ming;Zhao Qingzan;Ren Xiuhua;Li Zhihua;Cao Jing;Zang Weidong
目的糖皮质激素受体(GRs)是炎症反应中的活性调节因子。炎症反应在神经病理性疼痛中起着重要作用，但GR调节神经病理性疼痛炎症反应的机制尚不清楚。研究表明，GRs的激活参与了p38MAPK介导的转录抑制。GRs是否通过p38MAPK信号通路参与神经病理性疼痛的炎症反应是一个悬而未决的问题。主要方法采用大鼠备用神经损伤作为神经病理性疼痛的模型。用von Frey细丝进行痛敏实验。用免疫印迹和免疫荧光法检测GR、p-p38和NF-κB的表达。用双抗体夹心ELISA法检测脊髓组织中IL-6和肿瘤坏死因子-α的表达。鞘内注射p38MAPK拮抗剂SB203580可激活GR，降低NF-κB，自术后3 起疼痛减轻。鞘内注射糖皮质激素受体拮抗剂RU38486可拮抗SB203580对NF-κB表达及IL-6和α释放的影响。鞘内注射糖皮质激素受体激动剂地塞米松激活GR后，可抑制NF-κB的表达，抑制IL-6和α的释放，从而减轻疼痛。
AimsThe glucocorticoid receptors (GRs) are an active regulator in inflammatory responses. The inflammatory reaction plays an important role in neuropathic pain, but the underlying mechanisms that GR regulates the inflammatory responses in neuropathic pain are still unknown. The activation of GRs has been shown to participate in the p38MAPK-mediated suppression of transcription activation. An unanswered question is whether GRs take part in inflammatory responses in neuropathic pain through p38MAPK signaling pathway.Main methodsThe spared nerve injury (SNI) in rats was used as a model of neuropathic pain. Pain sensitivity was tested by von Frey filaments. The expression of GR, p-p38 and NF-κB were detected by Western blot and immunofluorescence. Elisa was used to examine the expression of IL-6 and TNF-α.Key findingsNerve injury led to p38 activation and GR expression decline in spinal cord of SNI rats. Intrathecal injection of the p38MAPK antagonist SB203580 activated GR and decreased NF-κB, resulting in pain relief since 3 days post-operation in SNI rats. Moreover, Intrathecal injection of the GR antagonist RU38486 counteracted the effect of SB203580 on NF-κB expression along with the release of IL-6 and TNF-α. On the contrary, activation of the GR by intrathecal administration of dexamethasone, a GR agonist, inhibited the expression of NF-κB and the release of IL-6 and TNF-α, resulting in pain relief.SignificanceActivation of p38MAPK in spinal cord could downregulate the GR expression and thereby activate NF-κB, thus promoting the release of IL-6 and TNF-α and participating in the development of neuropathic pain.