脊髓谷氨酸转运体1对大鼠坐骨神经慢性压迫损伤及吗啡耐受的影响

为了探讨脊髓谷氨酸转运体1 (GLT-1) 的表达量和活性状态与吗啡耐受和神经源性痛的关系，利用大鼠坐骨神经慢性压迫损伤 (CCI) 模型，以机械性缩足痛阈值 (MWT) 为评估指标，谷氨酸转运体激动剂β内酰胺类抗生素头孢曲松钠为工具药，观察对大鼠机械痛敏和吗啡耐受的影响；以实时定量PCR及Western blotting考察脊髓GLT-1表达水平的变化。结果表明，CCI大鼠在术后1周与对照组相比MWT值下降约80%；CCI大鼠单独使用吗啡产生快速耐受，给药第3天与CCI模型对照组大鼠比较MWT值已无明显差异，脊髓GLT-1表达也明显下调；单独使用头孢曲松钠对痛敏有改善作用，脊髓GLT-1表达明显上调；吗啡伴随头孢曲松钠给药组耐受速度明显减慢，给药6天后MWT值仍保持在较高水平，与CCI吗啡耐受组比较有显著性差异，GLT-1表达明显上调。因此，脊髓GLT-1活性变化与神经源性痛及吗啡耐受的形成密切相关，促进GLT-1功能可显著延缓吗啡耐受与痛敏形成。

Effect of spinal glutamate transporter 1 on chronic constriction injury of sciatic nerve and morphine tolerance of rats

In order to investigate the role of spinal glutamate transporter 1 (GLT-1) in the neuropathic   pain and morphine tolerance, rat chronic constriction injury (CCI) of sciatic nerve was performed, and the    mechanical allodynia was evaluated by mechanical withdrawal threshold (MWT), the expression of GLT-1 was measured by real-time PCR and Western blotting analysis.  The results showed that compared to sham group, the MWT of CCI group had decreased approximately 80%.  Administration of morphine alone could develop tolerance rapidly in initial two days, and then had no significant difference with CCI group, the expression of GLT-1 was down-regulated.  Ceftriaxone sodium alone could improve mechanical allodynia.  Co-administration of ceftriaxone sodium with morphine attenuated morphine tolerance and up-regulated GLT-1 expression, and the MWT remained at high level after 6 days.  In conclusion, change of spinal GLT-1 expression and function has close correlation with the development of neuropathic pain and morphine tolerance.