中文摘要：

目的研究脊髓蛋白酪氨酸磷酸酶（protein tyrosine phosphatases,PTPs）在炎性疼痛中的作用及其机制。方法昆明种♂小鼠,左后足底皮下注射完全弗氏佐剂（CFA）,建立炎性疼痛动物模型;24 h后,鞘内给予PTPs抑制剂正钒酸钠（sodium orthovanadate,Na3VO4）,观察对缩足阈值的影响;免疫印迹法检测正钒酸钠对损伤侧脊髓背角NMDA受体NR2B亚基第1472位酪氨酸（NR2B-Y1472）磷酸化水平的影响。结果鞘内注射正钒酸钠50、100和200 ng,虽然不影响正常动物的痛阈,但却能够剂量依赖性地缓解CFA诱发的机械性痛觉超敏,给药后30 min,炎性疼痛小鼠的缩足阈值从（0.24±0.07）g分别升高至（0.17±0.06）g（P〉0.05,n=4）、（1.07±0.51）g（P〈0.05,n=4）和（1.38±0.47）g（P〈0.05,n=4）;同时,CFA诱发的脊髓NR2B-Y1472的磷酸化也被正钒酸钠100 ng所完全阻断。结论 PTPs抑制剂正钒酸钠,通过降低脊髓NR2B的酪氨酸磷酸化,逆转炎性疼痛动物的NMDA受体功能亢进,产生明显的镇痛作用。

英文摘要：

Aim To investigate the role of spinal protein tyrosine phosphatases（PTPs） in inflammatory pain and its underlying mechanisms.Methods Complete Freund＇s Adjuvant（CFA） was intradermally injected into the left hindpaw of male Kunming mice to induce inflammatory pain.PTPs inhibitor sodium orthovanadate was intrathecally given one day after CFA injection to observe the alterations of Paw Withdrawal Threshold（PWT） values and of the phosphorylation of NMDA receptor NR2B subunit at Tyrosine 1472（NR2B-Y1472） in ipsilateral dorsal horn.Results Although intrathecal application of sodium orthovanadate for 30 min had no influence on PWT values in intact mice,it dose-dependently alleviated CFA-induced mechanical allodynia by elevating PWT values from（0.24±0.07） g（n=4） of inflamed mice to（0.17±0.06） g（50 ng,P0.05,n=4）,（1.07±0.51） g（100 ng,P0.05,n=4） and（1.38±0.47） g（200 ng,P0.05,n=4） respectively.Meanwhile,CFA-induced phosphorylation of NR2B-Y1472 was also repressed by sodium orthovanadate（100 ng）.Conclusions PTPs inhibitor sodium orthovanadate reverses NMDA receptor hyperfunction by suppressing NR2B tyrosine phosphorylation,leading to the amelioration of inflammatory pain.