文献类型：期刊文献

中文题名：TRPM3的酪氨酸磷酸化参与糖尿病诱发的热痛觉过敏

英文题名：Tyrosine phosphorylation of TRPM3 ion channel mediates diabetes-induced heat hyperalgesia

作者：杨丽[1];柏虎虎[2];贺沙沙[1];金月[1];刘成松[1]

第一作者：杨丽

机构：[1]甘肃中医药大学附属医院药学部,甘肃兰州730000;[2]兰州大学生命科学学院,甘肃兰州730000

第一机构：甘肃中医药大学第二附属医院

年份：2022

卷号：27

期号：9

起止页码：971

中文期刊名：中国临床药理学与治疗学

外文期刊名：Chinese Journal of Clinical Pharmacology and Therapeutics

收录：CSTPCD;;CSCD:【CSCD_E2021_2022】；

基金：甘肃省中医药管理局科研课题(GZK-2018-12)。

语种：中文

中文关键词：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

外文关键词：TRPM3;DRG;diabetic peripheral neuropathy;tyrosine phosphorylation;hyperalgesia;allodynia

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。
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.