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CX3CR1 contributes to streptozotocin-induced mechanical allodynia in the mouse spinal cord

CX3CL1 受体参与 1 型糖尿病机械痛的形成

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摘要

目 的

趋化因子 (CX3CL1) 在神经性疼痛中起重要的生理病理作用, 然而其在糖尿病神经病理痛中的作用还有待研究。 本实验主要研究了在糖尿病小鼠痛阈下调的时间窗内, 脊髓背角中趋化因子 CX3CL1/趋化因子受体 (CX3CR1) 在触诱发痛发生与发展中的作用。

创新点

主要探讨 CX3CR1 在链脲佐菌素 (STZ) 诱导的 1 型糖尿病 (T1DM) 小鼠早期发生的机械痛性神经病变中的作用。

方 法

本实验采用健康雄性 C57BL/6 小鼠与 CX3CR1 KO 小鼠, 体重 20∼30 g, 隔夜禁食12 h (20 点至次日 8 点), 并连续三天腹腔注射 100 mg/kg 的 STZ 制备 T1DM 模型。 以空腹血糖浓度>11.1 mmol/L 且三周后小鼠机械痛阈值明显下降的情况视为 T1DM 模型制备成功。在小鼠机械痛阈下降的对 应时间点, 取腰段脊髓背角, 采用蛋白质印迹法 (western blot) 和免疫组化法测定 CX3CL1 及 CX3CR1 的表达情况。 同时, 在发生机械痛阈值下降的第三周时间鞘内给予 CX3CR1 的中和抗体, 进行机械刺激并观察其痛阈值的变化。

结 论

STZ 诱导的 T1DM 动物模型在早期表现为显著的 机械诱发痛, 并伴随脊髓背角 CX3CL1/CX3CR1 表达上调; 在痛阈下降期鞘内给予 CX3CR1 的中 和抗体可抑制糖尿病小鼠的痛行为。 与腹腔注射 STZ 形成 T1DM 的 C57BL/6 小鼠相比 CX3CR1 基因敲除的糖尿病小鼠机械痛阈值下降的时间 延迟, 程度减轻。 因此, 我们推测 CX3CL1/CX3CR1 可能参与 T1DM 机械痛的形成与发展。

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Acknowledgments

We thank Prof. Zhi-qi ZHAO (Institutes of Brain Science, Fudan University, Shanghai, China) for his helpful criticism and advice to this work.

Author information

Cheng-ming NI and Bing-yu LING were responsible for drafting the manuscript, and analysis and interpretation of data. Xiang XU collected and analyzed the data. He-ping SUN and Hui JIN contributed analysis of data and manuscript preparation. Yu-qiu ZHANG helped perform the analysis with constructive discussions. Hong CAO and Lan XU contributed the conception and design of the current study. All authors have read and approved the final manuscript. Therefore, all authors have full access to all the data in the study and take responsibility for the integrity and security of the data.

Correspondence to Hong Cao or Lan Xu.

Ethics declarations

Cheng-ming NI, Bing-yu LING, Xiang XU, He-ping SUN, Hui JIN, Yu-qiu ZHANG, Hong CAO, and Lan XU declare that they have no conflict of interest.

All institutional and national guidelines for the care and use of laboratory animals were followed. All experiments were approved by the Animal Care and Use Committee of Fudan University, Shanghai, China and followed the policies issued by the guidelines for pain research of the International Association for the Study of Pain (IASP).

Additional information

Project supported by the National Natural Science Foundation of China (Nos. 81771208 and 81971043), the Health and Family Planning Commission of Wuxi (No. YGZXM1406), the Wuxi Municipal Bureau on Science and Technology (No. CSE31N1614), the Fundamental Research Fund of Wuxi People’s Hospital (No. RKA201720), and the Technology for Social Development Project of Kunshan (No. KS1539), China

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Ni, C., Ling, B., Xu, X. et al. CX3CR1 contributes to streptozotocin-induced mechanical allodynia in the mouse spinal cord. J. Zhejiang Univ. Sci. B (2020). https://doi.org/10.1631/jzus.B1900439

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关键词

  • 趋化因子(CX3CL1)
  • 趋化因子受体(CX3CR1)
  • 机械痛
  • 链脲佐菌素
  • 糖尿病模型