|
| 鞘内注射Maresin 1对骨癌痛小鼠痛行为学和脊髓胶质细胞活化的影响 |
| Intrathecal administration of Maresin 1 attenuates bone cancer pain by inhibiting the glial cells activation and neuroinflammation in the spinal cord |
| |
| DOI：10.12089/jca.2023.11.012 |
| 中文关键词: 骨癌痛 特异性促炎症消退介质 鞘内注射 胶质细胞 炎症反应 |
| 英文关键词: Bone cancer pain Specialized pro-resolving mediators Intrathecal administration Glial cells Inflammation |
| 基金项目: |
|
| 摘要点击次数: 570 |
| 全文下载次数: 227 |
| 中文摘要: |
目的 探讨鞘内注射Maresin 1对骨癌痛（BCP）小鼠痛行为学和脊髓胶质细胞活化的影响。
方法 实验一：选择清洁级健康雄性C57BL/6小鼠28只，4～6周龄，体质量18～22 g。随机分为两组：假手术1组（S1组）和BCP1组（B1组），每组14只。 B1组小鼠股骨髓腔内注射含有2×105个Lewis肺癌细胞的PBS溶液20 μl，建立骨癌痛小鼠模型；S1组仅注射PBS溶液20 μl。造骨癌痛模型（造模）前1 d、造模后3、7、10、14和21 d时随机取6只测定机械缩足阈值（MWT）和热缩足潜伏期（TWL）。B1组和S1组于造模后7、14和21 d时随机取4只小鼠处死，采用Western blot法检测脊髓胶质纤维酸性蛋白（GFAP）和离子钙结合适配器分子1（Iba1）含量。实验二：清洁级健康雄性C57BL/6小鼠36只，随机分为三组：假手术2组（S2组）、BCP2组（B2）组和Maresin 1（M）组，每组12只。S2组注射PBS溶液20 μl；B2和M组造骨癌痛小鼠模型。M组于造模后14～16 d时连续3 d鞘内注射Maresin 1 50 ng/5 μl。S2组、B2组和M组于造模后14～18 d时随机取6只测定MWT和TWL。于造模后18 d行为学测试完成后处死小鼠，采用Western blot和免疫荧光法检测脊髓GFAP和Iba1含量。ELISA法检测脊髓IL-1β、IL-6和TNF-α浓度。
结果 实验一：与S1组比较，B1组造模后7、10、14和21 d MWT明显降低，TWL明显缩短，造模后7、14和21 d脊髓GFAP和Iba1含量明显升高（P＜0.05）。实验二：与S2组比较，B2组造模后18 d脊髓GFAP和Iba1含量明显升高，平均荧光强度明显增强，脊髓IL-1β、IL-6和TNF-α浓度明显升高（P＜0.05）。与B2组比较，M组造模后15～18 d时MWT明显升高，TWL明显延长（P＜0.05），造模后18 d脊髓GFAP和Iba1含量明显降低，平均荧光强度明显减弱（P＜0.05），脊髓IL-1β、IL-6和TNF-α浓度明显降低（P＜0.05）。
结论 鞘内注射Maresin 1可能通过抑制脊髓胶质细胞活化，减轻神经炎症反应，缓解骨癌痛。 |
| 英文摘要: |
Objective To investigate the effects of intrathecal administration of Maresin 1 on pain behavior and glial cells activation in spinal dorsal horn of mice with bone cancer pain (BCP).
Methods Experiment Ⅰ, twenty-eight clean male C57BL/6 mice, aged 4-6 weeks, weighing 18-22 g, were randomly divided into two groups: sham 1 group (group S1) and BCP 1 group (group B1), 14 mice in each group. BCP model was established in group B1 by injecting PBS 20 μl containing 2 × 105 lewis lung carcinoma cells into the intramedullary space. Group S1 received PBS 20 μl without tumor cells. Six mice in each group were randomly selected to determine the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) 1 day before implantation, 3, 7, 14, 21 days after implantation. Four mice were randomly sacrificed on days 7, 14 and 21 in group S1 and group B1. The expressions of spinal glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1(Iba1) were detected by Western blot. Experiment Ⅱ,thirty-six clean male C57BL/6 mice were randomly divided into three groups: sham 2 group (group S2), BCP 2 group (group B2), and Maresin 1 group (group M), 12 mice in each group. BCP models were established in groups B2 and M while group S2 received PBS 20 μl without tumor cells. Maresin 1 50 ng/5 μl were intrathecally injected from days 14 to 16 after tumor cells implantation. Six mice in each group were randomly selected to determine the MWT and TWL on days 14 to 18 after implantation. Mice were sacrificed on day 18 after pain behavior tests. The expressions of spinal GFAP and Iba1 were detected by Western blot and immunofluorescence staining. The levels of spinal IL-1β, IL-6,and TNF-α were detected by ELISA.
Results Experiment Ⅰ: compared with group S1,the MWT and TWL were significantly lower on days 7, 10, 14, and 21 after implantation in group B1(P < 0.05), the expressions of spinal GFAP and Iba1 were upregulated on days 7, 14, and 21 after implantation in group B1(P < 0.05). Experiment Ⅱ: compared with group S2, the levels of spinal GFAP, Iba1, IL-1β, IL-6, and TNF-α were increased on day 18 after implantation in group B2(P < 0.05). Compared with group B2, the MWT and TWL were significantly higher on days 15-18 after implantation while levels of spinal GFAP, Iba1, IL-1β, IL-6, and TNF-α on day 18 were decreased in group M (P < 0.05).
Conclusion Intrathecal administration of Maresin 1 attenuates BCP maybe by inhibiting the glial cells activation and neuroinflammation in the spinal cord. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
