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中国临床药理学与治疗学 ›› 2022, Vol. 27 ›› Issue (9): 971-976.doi: 10.12092/j.issn.1009-2501.2022.09.002

• 基础研究 • 上一篇    下一篇

TRPM3的酪氨酸磷酸化参与糖尿病诱发的热痛觉过敏

杨丽1,柏虎虎2,贺沙沙1,金月1,刘成松1   

  1. 1甘肃中医药大学附属医院药学部,兰州 730000,甘肃;2兰州大学生命科学学院,兰州 730000,甘肃
  • 收稿日期:2022-04-29 修回日期:2022-09-06 出版日期:2022-09-27 发布日期:2022-10-14
  • 通讯作者: 刘成松,男,硕士,主任药师,研究方向:药学。 E-mail: 764804252@qq.com
  • 作者简介:杨丽,女,硕士,主管药师,研究方向:难治性疼痛的治疗。 E-mail: yuankeyangli@163.com
  • 基金资助:
    甘肃省中医药管理局科研课题(GZK-2018-12)

Tyrosine phosphorylation of TRPM3 ion channel mediates diabetes-induced heat hyperalgesia

YANG Li1, BAI Huhu2, HE Shasha1, JIN Yue1, LIU Chengsong1   

  1. Department of pharmacy, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000,Gansu, China
  • Received:2022-04-29 Revised:2022-09-06 Online:2022-09-27 Published:2022-10-14

摘要: 目的:探讨TRPM3与糖尿病诱发的痛觉敏化的关系。方法:小鼠腹腔注射链脲佐菌素Streptozotocin(STZ)建立糖尿病模型,测定痛觉阈值观察糖尿病小鼠的行为学改变;使用免疫共沉淀以及免疫印迹法,探讨背根神经节(dorsal root ganglia, DRG)中TRPM3的蛋白含量及其磷酸化修饰在痛觉调控中的作用。结果:糖尿病模型小鼠的机械性缩足阈值(paw withdraw thresholds, PWTs)和热缩足潜伏期(paw withdraw latencies, PWLs)显著下降;糖尿病小鼠DRG中TRPM3酪氨酸磷酸化水平较对照组显著升高,而蛋白表达基本不变;在正常小鼠的DRG注射BPV提高TRPM3的酪氨酸磷酸化水平,可诱发热痛觉过敏;DRG注射PP2降低糖尿病模型小鼠TRPM3的酪氨酸磷酸化水平后,小鼠热痛觉过敏缓解,而机械性痛觉超敏不受影响。 结论:TRPM3的酪氨酸磷酸化修饰,参与糖尿病诱发的热痛觉过敏。

关键词: TRPM3, 背根神经节, 糖尿病周围神经病变, 酪氨酸磷酸化, 痛觉过敏

Abstract: AIM: To investigate the relationship between TRPM3 and diabetes-induced painful peripheral neuropathy.  METHODS: Treptozotocin (STZ) was intraperitoneal injected for establishment of diabetic mice model, behavioral tests of paw withdraw thresholds (PWTs) and paw withdraw latencies (PWLs) were conducted; Protein contents and tyrosine phosphorylation levels of TRPM3 were detected by immunoprecipitation and immunoblotting. RESULTS: The PWTs and PWLs in diabetic mice were significantly reduced; TRPM3 tyrosine phosphorylation in the dorsal root ganglia (DRG) of diabetic mice significantly increased compared with control, while the protein expression shows no statistical significance; Enhanced tyrosine phosphorylation of TRPM3 by BPV can evoke heat hyperalgesia in intact mice; Reduce of the tyrosine phosphorylation levels of TRPM3 through PP2 significantly alleviates diabetes-induced heat hyperalgesia, without affecting mechanical allodynia. CONCLUSION: The upregulation of tyrosine phosphorylation of TRPM3 plays a key role in heat related painful diabetic peripheral neuropathy.

Key words: TRPM3, DRG, diabetic peripheral neuropathy, tyrosine phosphorylation, hyperalgesia, allodynia

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