• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

核因子E2相关因子2/抗氧化反应元件的激活减轻了硝酸甘油诱导的大鼠痛觉过敏。

Activation of the nuclear factor E2-related factor 2/anitioxidant response element alleviates the nitroglycerin-induced hyperalgesia in rats.

作者信息

Di Wei, Shi Xiaolei, Lv Hua, Liu Jun, Zhang Hong, Li Zhiwei, Fang Yannan

机构信息

Department of Neurology, Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, 710068, China.

Department of Neurology, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Anhui, 241001, China.

出版信息

J Headache Pain. 2016 Dec;17(1):99. doi: 10.1186/s10194-016-0694-x. Epub 2016 Oct 24.

DOI:10.1186/s10194-016-0694-x
PMID:27778243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5078120/
Abstract

BACKGROUND

Antioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats.

METHODS

The expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot. Immunofluorescence was used to demonstrate the cell-specific localization of Nrf2 in TNC. Sulforaphane, a Nrf2 activator, was administered to NTG-induced rats. Then, the number of c-Fos- and nNOS-immunoreactive neurons in TNC was evaluated using immunofluorescence, and c-Fos and nNOS protein levels were quantified using western blot. Von Frey hair testing was used to evaluate the tactile thresholds of rats at different time points in different groups.

RESULTS

Total cellular and nuclear levels of the proteins Nrf2, HO1, and NQO1 were elevated in TNC after NTG injection, and Nrf2 was found to be located in the nucleus and cytoplasm of the neurons. Sulforaphane pretreatment significantly increased the nuclear Nrf2, HO1, and NQO1 levels in TNC. In addition, sulforaphane exposure effectively inhibited the expression of nNOS and c-Fos, reduced the number of nNOS and c-Fos immunoreactive neurons in TNC, and attenuated the tactile thresholds induced by NTG injection.

CONCLUSION

Oxidative stress was involved in nitroglycerin-induced hyperalgesia. Activation of the Nrf2/ARE pathway inhibited the activation of TGVS and prevented the induction of hyperalgesia. Sulforaphane might therefore be an effective agent for hyperalgesia. Further studies are needed to discover the underlying mechanisms of the process.

摘要

背景

抗氧化剂已被证明可减轻神经性疼痛中的痛觉过敏。内源性抗氧化防御系统可能在预防偏头痛中的痛觉过敏方面发挥作用。在本研究中，我们旨在评估核因子E2相关因子2/抗氧化反应元件（Nrf2/ARE）通路在调节三叉神经血管系统（TGVS）激活及硝酸甘油（NTG）诱导的痛觉过敏大鼠超敏反应中的作用。

方法

采用蛋白质免疫印迹法检测三叉神经脊束核（TNC）中Nrf2、HO、HO1和NQO1的表达水平。利用免疫荧光法显示Nrf2在TNC中的细胞特异性定位。将Nrf2激活剂萝卜硫素给予NTG诱导的大鼠。然后，使用免疫荧光法评估TNC中c-Fos和nNOS免疫反应性神经元的数量，并通过蛋白质免疫印迹法定量c-Fos和nNOS蛋白水平。使用von Frey毛发测试评估不同组大鼠在不同时间点的触觉阈值。

结果

NTG注射后，TNC中Nrf2、HO1和NQO1蛋白的总细胞水平和核水平升高，且发现Nrf2位于神经元细胞核和细胞质中。萝卜硫素预处理显著增加了TNC中核Nrf2、HO1和NQO1水平。此外，萝卜硫素暴露有效抑制了nNOS和c-Fos的表达，减少了TNC中nNOS和c-Fos免疫反应性神经元的数量，并减弱了NTG注射诱导的触觉阈值。

结论

氧化应激参与了硝酸甘油诱导的痛觉过敏。Nrf2/ARE通路的激活抑制了TGVS的激活并预防了痛觉过敏的诱导。因此，萝卜硫素可能是一种治疗痛觉过敏的有效药物。需要进一步研究以发现该过程的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/077066b8b340/10194_2016_694_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/33ff70a1e797/10194_2016_694_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/aee1d4745fc3/10194_2016_694_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/5d6da3ab4ae8/10194_2016_694_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/7c92b3b3f422/10194_2016_694_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/f126ac594d37/10194_2016_694_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/1fc6284fa5d6/10194_2016_694_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/077066b8b340/10194_2016_694_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/33ff70a1e797/10194_2016_694_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/aee1d4745fc3/10194_2016_694_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/5d6da3ab4ae8/10194_2016_694_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/7c92b3b3f422/10194_2016_694_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/f126ac594d37/10194_2016_694_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/1fc6284fa5d6/10194_2016_694_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09d6/5078120/077066b8b340/10194_2016_694_Fig7_HTML.jpg

相似文献

1
Activation of the nuclear factor E2-related factor 2/anitioxidant response element alleviates the nitroglycerin-induced hyperalgesia in rats.核因子E2相关因子2/抗氧化反应元件的激活减轻了硝酸甘油诱导的大鼠痛觉过敏。
J Headache Pain. 2016 Dec;17(1):99. doi: 10.1186/s10194-016-0694-x. Epub 2016 Oct 24.
2
Utility of different outcome measures for the nitroglycerin model of migraine in mice.不同结局指标在小鼠偏头痛硝酸甘油模型中的效用
J Pharmacol Toxicol Methods. 2016 Jan-Feb;77:33-44. doi: 10.1016/j.vascn.2015.09.006. Epub 2015 Oct 9.
3
Pregabalin alleviates the nitroglycerin-induced hyperalgesia in rats.普瑞巴林可减轻大鼠体内硝酸甘油诱导的痛觉过敏。
Neuroscience. 2015 Jan 22;284:11-17. doi: 10.1016/j.neuroscience.2014.08.056. Epub 2014 Oct 5.
4
TLR2 Mediates Microglial Activation and Contributes to Central Sensitization in a Recurrent Nitroglycerin-induced Chronic Migraine Model.TLR2 介导小胶质细胞活化，并在复发性硝酸甘油诱导的慢性偏头痛模型中导致中枢敏化。
Mol Neurobiol. 2024 Jun;61(6):3697-3714. doi: 10.1007/s12035-023-03781-2. Epub 2023 Nov 27.
5
Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation.一氧化氮合酶、降钙素基因相关肽和NK-1受体机制参与了硝酸甘油诱导的神经元激活。
Cephalalgia. 2014 Feb;34(2):136-47. doi: 10.1177/0333102413502735. Epub 2013 Sep 2.
6
Microglia P2X4R-BDNF signalling contributes to central sensitization in a recurrent nitroglycerin-induced chronic migraine model.小胶质细胞 P2X4R-BDNF 信号转导参与硝酸甘油诱导的复发性偏头痛慢性模型中的中枢敏化。
J Headache Pain. 2020 Jan 14;21(1):4. doi: 10.1186/s10194-019-1070-4.
7
Systemic nitroglycerin increases nNOS levels in rat trigeminal nucleus caudalis.全身性硝酸甘油可增加大鼠三叉神经脊束核中的神经元型一氧化氮合酶水平。
Neuroreport. 2000 Sep 28;11(14):3071-5. doi: 10.1097/00001756-200009280-00008.
8
Microglia P2X4 receptor contributes to central sensitization following recurrent nitroglycerin stimulation.小胶质细胞 P2X4 受体在反复硝酸甘油刺激后导致中枢敏化。
J Neuroinflammation. 2018 Aug 30;15(1):245. doi: 10.1186/s12974-018-1285-3.
9
Microglial NLRP3 inflammasome activation mediates IL-1β release and contributes to central sensitization in a recurrent nitroglycerin-induced migraine model.小胶质细胞 NLRP3 炎性体激活介导白细胞介素-1β释放，并有助于复发性硝酸甘油诱导偏头痛模型中的中枢敏化。
J Neuroinflammation. 2019 Apr 10;16(1):78. doi: 10.1186/s12974-019-1459-7.
10
Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine.降钙素基因相关肽促进慢性偏头痛大鼠模型前庭核敏化。
J Headache Pain. 2020 Jun 10;21(1):72. doi: 10.1186/s10194-020-01145-y.

引用本文的文献

1
Poly-IC Alleviates Nitroglycerin-Induced Migraine by Inhibiting Neuroinflammation via TLR3/TRIF Signaling Pathway.聚肌胞苷酸通过TLR3/TRIF信号通路抑制神经炎症来减轻硝酸甘油诱导的偏头痛。
CNS Neurosci Ther. 2025 May;31(5):e70444. doi: 10.1111/cns.70444.
2
Impact of genetic polymorphisms on associations between crude oil exposure and health effects among Coast Guard Deepwater Horizon responders.基因多态性对海岸警卫队“深水地平线”事件响应者原油暴露与健康影响之间关联的影响。
Sci Total Environ. 2024 Dec 20;957:177542. doi: 10.1016/j.scitotenv.2024.177542. Epub 2024 Nov 30.
3
Targeting Nrf2 signaling in dry eye.

本文引用的文献

1
Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.无机砷在体内诱导大脑皮层和海马体中NRF2调节的抗氧化防御。
Neurochem Res. 2016 Aug;41(8):2119-28. doi: 10.1007/s11064-016-1927-8. Epub 2016 May 10.
2
Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-кB.丙戊酸盐通过抑制核因子κB改善大鼠三叉神经脊束核中硝酸甘油诱导的偏头痛。
J Headache Pain. 2016;17:49. doi: 10.1186/s10194-016-0631-z. Epub 2016 May 6.
3
Sulforaphane Attenuates Muscle Inflammation in Dystrophin-deficient mdx Mice via NF-E2-related Factor 2 (Nrf2)-mediated Inhibition of NF-κB Signaling Pathway.
针对干眼症中的Nrf2信号通路。
Int J Ophthalmol. 2024 Oct 18;17(10):1911-1920. doi: 10.18240/ijo.2024.10.19. eCollection 2024.
4
Unveiling the therapeutic potential of Dl-3-n-butylphthalide in NTG-induced migraine mouse: activating the Nrf2 pathway to alleviate oxidative stress and neuroinflammation.揭示 Dl-3-正丁基苯酞在硝酸甘油诱导偏头痛小鼠中的治疗潜力：激活 Nrf2 通路减轻氧化应激和神经炎症。
J Headache Pain. 2024 Apr 2;25(1):50. doi: 10.1186/s10194-024-01750-1.
5
Pharmacological Characterization of Orofacial Nociception in Female Rats Following Nitroglycerin Administration.硝酸甘油给药后雌性大鼠口腔面部伤害感受的药理学特征
Front Pharmacol. 2020 Dec 3;11:527495. doi: 10.3389/fphar.2020.527495. eCollection 2020.
6
Dimethyl fumarate alleviates the nitroglycerin (NTG)-induced migraine in mice.富马酸二甲酯可缓解硝酸甘油（NTG）诱导的小鼠偏头痛。
J Neuroinflammation. 2020 Feb 17;17(1):59. doi: 10.1186/s12974-020-01736-1.
7
Low-dose interleukin-2 reverses behavioral sensitization in multiple mouse models of headache disorders.低剂量白细胞介素-2可逆转多种头痛障碍小鼠模型中的行为敏化。
Pain. 2020 Jun;161(6):1381-1398. doi: 10.1097/j.pain.0000000000001818.
8
The neuroprotective mechanisms and effects of sulforaphane.萝卜硫素的神经保护机制及作用
Brain Circ. 2019 Apr-Jun;5(2):74-83. doi: 10.4103/bc.bc_7_19. Epub 2019 Jun 27.
9
Liposomal Curcumin Enhances the Effect of Naproxen in a Rat Model of Migraine.脂质体姜黄素增强萘普生在偏头痛大鼠模型中的作用。
Med Sci Monit. 2019 Jul 9;25:5087-5097. doi: 10.12659/MSM.915607.
10
Milk Fat Globule-Epidermal Growth Factor-Factor 8 Reverses Lipopolysaccharide-Induced Microglial Oxidative Stress.乳脂肪球表皮生长因子 8 逆转脂多糖诱导的小胶质细胞氧化应激。
Oxid Med Cell Longev. 2019 Mar 13;2019:2601394. doi: 10.1155/2019/2601394. eCollection 2019.
萝卜硫素通过NF-E2相关因子2（Nrf2）介导的对NF-κB信号通路的抑制作用减轻肌营养不良蛋白缺陷型mdx小鼠的肌肉炎症。
J Biol Chem. 2015 Jul 17;290(29):17784-17795. doi: 10.1074/jbc.M115.655019. Epub 2015 May 26.
4
Temporal activation of Nrf2 in the penumbra and Nrf2 activator-mediated neuroprotection in ischemia-reperfusion injury.半暗带中Nrf2的短暂激活以及Nrf2激活剂在缺血再灌注损伤中的神经保护作用。
Free Radic Biol Med. 2014 Jul;72:124-33. doi: 10.1016/j.freeradbiomed.2014.04.009. Epub 2014 Apr 15.
5
Effects of CGRP receptor antagonism in nitroglycerin-induced hyperalgesia.降钙素基因相关肽（CGRP）受体拮抗作用在硝酸甘油诱导的痛觉过敏中的效应
Cephalalgia. 2014 Jul;34(8):594-604. doi: 10.1177/0333102413517776. Epub 2013 Dec 23.
6
Cutaneous allodynia as a predictor of migraine chronification.皮肤痛觉过敏作为偏头痛慢性化的预测指标。
Brain. 2013 Nov;136(Pt 11):3489-96. doi: 10.1093/brain/awt251. Epub 2013 Sep 29.
7
Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast differentiation.Nrf2 缺乏诱导氧化应激，并促进 RANKL 诱导的破骨细胞分化。
Free Radic Biol Med. 2013 Dec;65:789-799. doi: 10.1016/j.freeradbiomed.2013.08.005. Epub 2013 Aug 14.
8
Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels.活性氧通过激活 TRPA1 和 TRPV1 通道增强大鼠脊髓背角神经元的兴奋性突触传递。
Neuroscience. 2013 Sep 5;247:201-12. doi: 10.1016/j.neuroscience.2013.05.023. Epub 2013 May 22.
9
Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection.Nrf2 和 II 相抗氧化酶在神经保护中的新兴作用。
Prog Neurobiol. 2013 Jan;100:30-47. doi: 10.1016/j.pneurobio.2012.09.003. Epub 2012 Sep 29.
10
Nrf2 as a converging node for cellular signaling pathways of gasotransmitters.Nrf2 作为气体信号转导途径细胞信号通路的汇聚节点。
Med Hypotheses. 2012 Sep;79(3):308-10. doi: 10.1016/j.mehy.2012.05.016. Epub 2012 Jun 6.