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| 背根神经节Sigma-1受体在大鼠神经病理性痛中的作用 |
| Role of Sigma-1 receptor in dorsal root ganglia of neuropathic pain rats |
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| DOI：10.12089/jca.2024.03.012 |
| 中文关键词: 神经病理性痛 背根神经节 Sigma-1受体 P2X3受体 |
| 英文关键词: Neuropathic pain Dorsal root ganglion Sigma-1 receptor P2X3 receptor |
| 基金项目:遵义市科学技术局基金引导项目［遵市科合HZ〔2019〕74号］；贵州省卫生健康委科学技术基金项目（gzwkj2021-271）；贵州省科技计划项目（黔科合基础-ZK〔2022〕一般637） |
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| 中文摘要: |
目的：探讨神经病理性痛大鼠背根神经节（DRG）中Sigma-1受体的作用以及Sigma-1受体对P2X3受体表达和功能的影响。
方法：选择健康SPF级SD雄性大鼠48只，7周龄，体重180～200 g。按照随机数字表法分为三组：假手术组（Sham组）、神经病理性痛组（CCI组）和Sigma-1受体拮抗剂BD-1047组（BD组），每组16只。鞘内置管后1 d，Sham组只游离右侧坐骨神经主干不结扎，CCI组、BD组制备神经病理性痛大鼠模型。模型制备后第1天起，每日上午08：00 Sham组和CCI组鞘内注射生理盐水30 μl，BD组鞘内注射120 nmol BD-1047 20 μl+生理盐水10 μl，连续14 d。于模型制备前1 d、模型制备后l、3、7、10、14 d鞘内给药后30 min测定热缩足潜伏期（TWL）和机械缩足反应阈值（MWT）。于模型制备后7 d采用Western blot法检测Sigma-1受体和P2X3受体蛋白含量。CCI组于模型制备后7、14 d采用免疫荧光双标技术和免疫共沉淀技术检测Sigma-1受体、P2X3受体共表达和共沉淀情况。
结果：与Sham组比较，CCI组模型制备后l、3、7、10、14 d TWL明显缩短，MWT明显降低，模型制备后7 d DRG组织Sigma-1受体和P2X3受体蛋白含量明显升高（P<0.05）。与CCI组比较，BD组模型制备后l、3、7、10、14 d TWL明显延长，MWT明显升高，模型制备后7 d DRG组织Sigma-1受体和P2X3受体蛋白含量明显降低（P<0.05）。模型制备后7、14 d CCI组中DRG组织Sigma-1受体与P2X3受体共表达、共沉淀。
结论：Sigma-1受体和P2X3受体在DRG中共表达，且存在共沉淀现象，抑制Sigma-1受体可以降低P2X3受体蛋白含量，缓解大鼠神经病理性痛。 |
| 英文摘要: |
Objective: To investigate the effect of Sigma-1 receptor activation in the dorsal root ganglia (DRG) of rats with neuropathic pain on the expression and function of P2X3 receptor.
Methods: Forty-eight healthy male SPF grade SD rats, aged 7 weeks, weighing 180-200 g, were randomly divided into three groups by using random number table method: sham operation group (group Sham), neuropathic pain group (group CCI), and Sigma-1 receptor antagonist BD-1047 group (group BD), 16 rats in each group. One day after the insertion of the sheath tube, group Sham only dissociated the right sciatic nerve trunk without ligation, while groups CCI and BD established neuropathic pain rat models. Starting from the first day after model established, normal saline 30 μl were intrathecal injected at 08:00 in groups Sham and CCI, while 120 nmol BD-1047 20 μl and normal saline 10 μl were intrathecal injected in group BD14 days continuously. Thermal contraction latency (TWL) and mechanical contraction response threshold (MWT) were measured 1 day before model established and 30 minutes after intrathecal administration on 1 day, 3, 7, 10, and 14 days after model established. Western blot was used to detect the protein content of Sigma-1 receptor and P2X3 receptor on 7 days after model established. Co-expression and co-precipitation of Sigma-1 receptor and P2X3 receptor were tested using immunofluorescence double labeling and immunoprecipitation techniques 7 and 14 days after model established in group CCI.
Results: Compared with group Sham, TWL and MWT were significantly decreased on 1 day, 3, 7, 10, and 14 days after model established, while the protein content of Sigma-1 receptor and P2X3 receptor in DRG was significantly increased on 7 days after model established in group CCI (P < 0.05). Compared with group CCI, TWL and MWT were significantly increased on 1 day, 3, 7, 10, and 14 days after model established, and the protein content of Sigma-1 receptor and P2X3 receptor in DRG was significantly decreased 7 days after model established in group BD (P < 0.05). Sigma-1 receptor and P2X3 receptor in DRG were co-expressed and co-precipitated in group CCI 7 and 14 days after model established.
Conclusion: Sigma-1 receptor and P2X3 receptor were co-expressed in DRG, and there was co-precipitation. Inhibition of Sigma-1 receptor could decrease P2X3 receptor protein content and alleviate neuropathic pain in rats. |
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