SHP2抑制剂NSC-87877对炎性疼痛的抑制作用及其机制  

Inhibitory effects of SHP2 blocker NSC-87877 on inflammatory pain and its underlying mechanisms

作　　者：杨鸿斌[1] 杨娴[1] 曹静[1] 李帅[1] 刘燕妮[1] 索占伟[1] 郑城容[1] 崔鸿斌[2] 郭忠[3] 胡晓东[1] 

机构地区：[1]兰州大学药学院分子药理研究所,兰州730000 [2]兰州大学第二医院急救中心,兰州730030 [3]西北民族大学医学院,兰州730030

出　　处：《中国药理学通报》2010年第9期1142-1145,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30870837);教育部"新世纪优秀人才支持计划"资助课题;兰州大学中央高校基本科研业务费专项资金资助(Nolzujbky-2009-99)

摘　　要：目的探讨蛋白酪氨酸磷酸酶SHP2(src homology-2 domain-containing phosphatase 2)的抑制剂NSC-87877对炎性疼痛的影响及其机制;方法小鼠左后足底皮下注射完全佛氏佐剂(Complete Freund's Adjuvant;CFA)建立疼痛模型;鞘内给予NSC-87877前后,测定缩足阈值;随后分离左侧L4-L5节段脊髓背角,免疫印迹法检测N-methyl-D-aspartate(NM-DA)型谷氨酸受体的表达;结果 SHP2广泛分布于脊髓背角;且SHP2抑制剂NSC-87877(3μg)能够抑制CFA诱发的痛觉超敏,而对正常动物的痛行为无作用。虽然NSC-87877不影响NMDA受体NR2B和NR2A亚基的总蛋白含量,但却能够特异性降低CFA组动物NR2B的突触表达水平;结论 SHP2抑制剂NSC-87877通过逆转NR2B的突触表达亢进,对炎性疼痛产生明显的抑制作用。Aim To investigate the effects of Src Homology-2 domain-containing Phosphatase 2（SHP2） blocker NSC-87877 on inflammatory pain and its underlying mechanisms.Methods Complete Freund＇s Adjuvant（CFA） was injected into the plantar surface of the left hindpaw of mice to induce inflammatory pain.Paw Withdrawal Threshold（PWT） was measured before and after intrathecal administration of NSC-87877.Immediately after behavioral tests,sinistral spinal dorsal horn at L4-L5 level was removed for immunoblotting analysis of the expression of NMDA receptors.Results SHP2 was widely distributed in spinal dorsal horn.SHP2 inhibitor NSC-87877（3 μg） alleviated CFA-induced mechanical allodynia,which had no effects on the nociceptive responses in naive mice.NSC-87877 specifically abolished the increase in the synaptic expression of NMDA receptor NR2B subunits in inflamed mice,with the total protein levels of NMDA receptor NR2A and NR2B subunits unaltered.Conclusion NSC-87877 can ameliorate inflammatory pain by inhibiting the synaptic accumulation of NR2B in spinal dorsal horn.

关 键 词：SHP2 NSC-87877 NMDA受体 炎性疼痛 脊髓背角 突触输送 磷酸酶 

分 类 号：R-332[医药卫生] R322.81