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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。
Objective To investigate the effect of src homology-2 domain-containing phosphatase 2 inhibitor NSC-87877 on inflammatory pain and its mechanism. Methods The mice were injected subcutaneously with complete Freund’s adjuvant (Complete Freund’s Adjuvant; CFA) to establish the pain model; intrathecal NSC-87877 before and after determination of contracting threshold; followed by left spinal cord dorsal horn L4-L5 segregation, Western blotting detection of N-methyl-D-aspartate -DA) glutamate receptor. Results SHP2 was widely distributed in dorsal horn of spinal cord. SHP2 inhibitor NSC-87877 (3μg) could inhibit CFA-induced hyperalgesia and had no effect on the pain behavior of normal animals. Although NSC-87877 did not affect the total protein content of NMDA receptor NR2B and NR2A subunits, NSC-87877 specifically decreased the synaptic level of NR2B in CFA-treated animals. Conclusions NSC-87877 can reverse NR2B synaptic activation , A significant inhibitory effect on inflammatory pain.