摘要
目的 探讨甘氨酸受体α3亚基(GlyR-α3)在术后痛中的作用。方法 小鼠皮肤和肌肉切开建立术后痛模型;测定术后痛模型小鼠的痛觉阈值和舔足时间,评估GlyR-α3的酪氨酸磷酸化是否参与术后痛;使用免疫共沉淀以及免疫印迹法,探讨术后痛发生后,GlyR-α3蛋白含量及其酪氨酸磷酸化的变化;使用Bosutinib抑制Src激酶活性,验证Src是否调节GlyR-α3的酪氨酸磷酸化。结果 术后疼痛模型小鼠的机械性缩足阈值(paw withdrawal thresholds, PWTs)和热缩足潜伏期(paw withdrawal latencies, PWLs)明显下降,同时舔足时间明显延长;手术侧小鼠DRG中GlyR-α3的酪氨酸磷酸化水平明显升高,而GlyR-α3蛋白含量没有明显差异;手术侧DRG中Src表达增加,且Src与GlyR-α3的相互作用增强;抑制Src激酶的活性有助于降低GlyR-α3的酪氨酸磷酸化水平,同时缓解了术后痛症状。结论 Src激酶通过增强GlyR-α3的酪氨酸磷酸化参与术后疼痛的发生。
Aim To investigate the role of GlyR-α3 in postoperative pain.Methods The model of postoperative pain was established by incision of mouse skin and muscle.Pain responses including paw withdrawal thresholds(PWTs),paw withdrawal latencies(PWLs)and licking toes time were conducted and recorded.Protein contents and tyrosine phosphorylation levels of GlyR-α3 were detected by co-immunoprecipitation and immunoblotting.Bosutinib was used to inhibit Src kinase activity to verify whether Src was involved in tyrosine phosphorylation of GlyR-α3.Results The PWTs and PWLs in postoperative pain model mice were significantly reduced,whereas the licking time increased significantly.The tyrosine phosphorylation level of GlyR-α3 in the dorsal root ganglia(DRG)from incision sidesignificantly increased compared with contralateral side,while the protein expression showed no statistical significance.The expression of Src in DRGincreased after operation,and the interaction between Src and GlyR-α3 was enhanced in ipsilateral DRG compared with contralateral side.Inhibition of Src kinase activity helped to reduce tyrosine phosphorylation of GlyR-α3 from DRG and alleviate postoperative pain symptoms.Conclusion Src kinase is involved in the development of postoperative pain by enhancing tyrosine phosphorylation of GlyR-α3.
作者
杨丽
柏虎虎
贺沙沙
邢思佳
刘成松
YANG Li;BAI Hu-hu;HE Sha-sha;XING Si-jia;LIU Cheng-song(Dept of Pharmacy,Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,China;School of Life Science,Lanzhou University,Lanzhou 730000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2024年第10期1879-1883,共5页
Chinese Pharmacological Bulletin
基金
甘肃省中医药科研课题(No GZKP-2022-18)
甘肃省科技厅青年科技基金(No 23JRRA1106)。
