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| 自噬在二甲双胍缓解小鼠切口痛中的作用 |
| Role of autophagy in metformin relieving incisional pain in a mouse model |
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| DOI：10.12089/jca.2019.04.019 |
| 中文关键词: 二甲双胍 自噬 切口痛 神经炎症 |
| 英文关键词: Metformin Autophagy Incisional pain Neuroinflammation |
| 基金项目:国家自然科学基金(81873954);南京市科技发展计划项目(201715033);南京市医学科技发展资金资助(QRX17019) |
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| 中文摘要: |
目的 探讨自噬在二甲双胍缓解小鼠切口痛中的作用。
方法 选择4～6周清洁级健康成年雄性ICR小鼠，体重18～22 g。采用随机数字表法分为5组:对照组（C组）、二甲双胍组（M组）、切口痛组（I组）、切口痛+二甲双胍组（IM组）、切口痛+二甲双胍+自噬抑制剂三甲基腺嘌呤组（MA组），每组8只。C组、M组不造模。I组、IM组及MA组小鼠建立切口痛模型。M组、IM组、MA组从造模当天开始腹腔注射二甲双胍200 mg/kg，每日重复给药至造模后7 d。C组每日同一时点腹腔注射等容量生理盐水。MA组每日于腹腔注射二甲双胍30 min前预给予30 mg/kg三甲基腺嘌呤。分别于造模前1 d，造模后1、3、5、7 d测定机械缩足阈值（MWT）；造模后30 d，深麻醉下处死小鼠，取L4—L6脊髓膨大节段组织，采用Western blot法测定促炎细胞因子IL-1β和TNF-α浓度，自噬相关蛋白LC3Ⅱ和p62蛋白含量。
结果 与造模前1 d比较，造模后1、3、5 d Ⅰ组、IM组和MA组MWT明显降低（P<0.05）。造模后1、3、5 d Ⅰ组、IM组、MA组MWT明显低于C组（P<0.05）；IM组MWT明显高于Ⅰ组（P<0.05）；MA组MWT明显低于IM组（P<0.05）。Ⅰ组IL-1β和TNF-α浓度明显高于C组（P<0.05）；IM组IL-1β和TNF-α浓度明显低于I组（P<0.05）；MA组IL-1β和TNF-α浓度明显高于IM组（P<0.05）。M组和I组LC3Ⅱ蛋白含量明显高于C组，p62蛋白含量明显低于C组（P<0.05）；IM组LC3Ⅱ蛋白含量明显高于I组，p62蛋白含量明显低于I组（P<0.05）；MA组LC3Ⅱ蛋白含量明显低于IM组，p62蛋白含量明显高于IM组（P<0.05）。
结论 二甲双胍可抑制脊髓的神经炎症反应，缓解小鼠切口痛，其作用机理可能是通过激活自噬改善神经炎症。 |
| 英文摘要: |
Objective To evaluate the effects of autophagy on metformin relieving incisional pain in a mouse model.
Methods SPF adult male ICR mice(aged 4 - 6 weeks, weighing 18 - 22 g) were divided into 5 groups by using random number table (n=8): control group (group C), metformin group (group M), plantar incision group (group I), plantar incision+metformin group (group IM), and plantar incision+metformin+autophagy inhibitor 3-methyladenine group (group MA). Group C and group M did not make models, while group I, group IM and group MA established incision pain model. Group M, group IM, and group MA were administered with metformin 200 mg/kg by intraperitoneal injection, while group C were administered with the same volume of normal saline by intraperitoneal injection. Group MA was pre-administered with 30 mg/kg 3-methyladenine 30 minutes before intraperitoneal injection of metformin. The above administration was repeated daily until the 7th day after modeling from the day of modeling. The mechanical withdraw threshold (MWT) was measured 1 day before and 1, 3, 5 and 7 d after the modeling. 3 days after modeling, the mice were executed under deep anesthesia, and the L4-L6 spinal cord enlarged segments were taken out. Western blot was used to detect expression quantity of IL-1β, TNF-α, LC3II and p62.
Results Compared with 1 d before modeling, the MWT of group I, group IM and group MA decreased significantly after modeling1, 3, 5 d (P < 0.05); At 1, 3, 5 d after modeling, the MWT of group I, group IM and group MA was significantly lower than that of group C (P < 0.05); The MWT of group IM was significantly higher than that of group I (P < 0.05); The MWT of MA group was significantly lower than that of group IM(P < 0.05). The contents of IL-1β and TNF-α in group I were significantly higher than those in group C (P < 0.05); The contents of IL-1β and TNF-α in group IM were significantly lower than those in group I (P < 0.05); The content of IL-1β and TNF-α in group MA was significantly higher than that in group IM (P < 0.05). In group M and group I, the content of LC3II was significantly higher than that in group C, and the content of p62 was significantly lower than that in group C (P<0.05). In group IM, the content of LC3II was significantly higher than that in group I, and the content of p62 was significantly lower than that in group I （P < 0.05）; In group MA, the content of LC3II was significantly lower than that in group IM, and the content of p62 was significantly higher than that in group IM (P < 0.05).
Conclusion The mechanism of metformin in relieving incisional pain may be that it reduces the neuroinflammation by activating autophagy. |
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