| 摘要: |
| 目的：探讨 Nrf2/HO-1 在硫化氢减轻神经病理性疼痛中的调控作用。方法：选择雄性 SD 大鼠 64 只，采用随机数字表法随机分为对照组（Con 组）、神经病理性疼痛组（SNL 组）、神经病理性疼痛 +NaHS 组（SNL+NaHS 组）和神经病理性疼痛 +NaHS+Nrf2 siRNA 组（SNL+siRNA+NaHS 组）4 组。神经病理性疼痛模型采用脊神经结扎法（SNL）完成。Con 组、SNL 组和 SNL+NaHS 组接受处理后 7 d，收集各组大鼠脊髓膨大处，部分组织进行核蛋白和 RNA 的提取进行 Nrf2 的检测，部分组织进行免疫荧光 IBA1 和 Nrf2 的共定位检测。4 组大鼠在给予处理后的 1、2、3、5 和 7 d 进行行为学的检测，结束后收集大鼠脊髓膨大处进行 IBA1、Nrf2 和 HO-1 蛋白的检测，部分组织匀浆进行炎症因子 TNF-α和IL-1β 的检测。结果：与 Con 组比较，SNL 大鼠机械痛敏减少，热痛敏缩短，Nrf2 核蛋白和 mRNA 表达增加，免疫荧光结果 Nrf2 和 IBA1 蛋白表达及共定位表达增加，总蛋白 IBA1、Nrf2 和 HO-1 蛋白表达增加，TNF-α 和 IL-1β 表达增加； 与 SNL 组相比，SNL+NaHS 组机械痛敏增加，热痛敏延长，Nrf2 核蛋白和 mRNA 表达进一步增加，免疫荧光结果示 Nrf2 和 IBA1 蛋白表达及共定位表达进一步增加，总蛋白 IBA 蛋白表达减少，Nrf2 和 HO-1 蛋白表达进一步增加，TNF-α和IL-1β 表达减少；与 SNL+NaHS 组比较，SNL+siRNA+NaHS 组机械痛敏减少，热痛敏缩短，总蛋白 IBA1 蛋白表达增加、Nrf2 和 HO-1 蛋白表达减少，TNF-α和 IL-1β 表达增加。结论：NaHS 对 SNL 导致的神经病理性疼痛小胶质细胞的激活， 是通过调节 Nrf2/HO-1 信号通路实现的。 |
| 关键词: 神经病理性疼痛 小胶质细胞 硫化氢 |
| DOI：10.3969/j.issn.1007-6948.2019.02.001 |
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| 基金项目: |
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| Regulation of Neuropathic Pain by H2S via Nrf2/HO-1 Pathway |
| TIAN Li-hua,HAN Huan-zhi,ZHANG Yang,XIE Ke-liang,CHEN Hong-guang |
| Department of Pain, Wuqing Hospital of Ttraditional Chinese Medicine of Tianjin City, Tianjin (301700), China |
| Abstract: |
| Objective To investigate the regulated role of Nrf2 /HO- 1 on H 2 S alleviating the microglia activation in neuropathic pain in rats. Methods Sixty-four adult male Sprague-Dawley rats were randomly divided into four groups: control group (group Con, n = 16 ), neuropathic pain group (group SNL, n = 16 ), neuropathic pain+NaHS group (group SNL+NaHS, n = 16 ) and neuropathic pain+NaHS+Nrf 2 siRNA group (SNL+siRNA+NaHS, n=16). The animal model of neuropathic pain was performed by spinal nerve ligation (SNL). The L5-6 spine cords were collected for the detection of Nrf2 protein and Nrf2 mRNA by Western blotting and RT-PCR and IBA1 and Nrf2 co-location by immuno?uorescence after 7 d of administration in group Con, group SNL and group SNL+NaHS. After 1 , 2 , 3 , 5 and 7 d of operation, MWT and TWL were measured, and after detection of behavioristics, the L5-6 spine cords were collected for the detection of IBA1, Nrf2 and HO-1 protein by Western blotting and cytokines TNF-α and IL-1β by ELISA. Results Compared with group Con, MWT and TWL were reduced, Nrf2 nucleoprotein and mRNA, co-location of Nrf2 and IBA1 expression, total protein IBA1, Nrf2 and HO-1, and cytokines TNF-α and IL-1β were increased in group SNL; compared with group SNL, MWT and TWL were improved in group SNL+NaHS; compared with group SNL+NaHS, MWT and TWL were reduced, Nrf2 nucleoprotein and mRNA, the co-location of Nrf2 and IBA1 expression, total protein Nrf 2 and HO- 1 , were reduced, and total protein IBA1, cytokines TNF-α and IL-1β were increased in group SNL+NaHS+siRNA. Conclusion NaHS could alleviate the microglia activation by Nrf2/HO-1 pathway in neuropathic pain. |
| Key words: Neuropathic pain microglia H2S |
