鞘内注射米诺环素对神经病理性疼痛大鼠脊髓NMDAR1表达的影响  

INTRATHECAL MINOCYCLINE ON SPINAL NMDA RECEPTOR 1 SUBUNIT EXPRESSION IN RAT MODELS OF NEUROPATHIC PAIN

作　　者：杨美蓉[1] 江伟[2] 杜冬萍[1] 

机构地区：[1]上海交通大学附属上海市第六人民医院疼痛诊疗专科,上海200233 [2]上海交通大学附属上海市第六人民医院麻醉科,上海200233

出　　处：《中国疼痛医学杂志》2008年第5期278-281,共4页Chinese Journal of Pain Medicine

基　　金：上海市浦江人才计划基金资助项目(06P514065)

摘　　要：目的：观察鞘内注射特异性小胶质细胞抑制剂米诺环素对神经病理性疼痛大鼠机械痛阈和脊髓NMDAR1受体表达的影响。方法：结扎腰5神经根（SNL）建立大鼠神经病理性疼痛模型。雄性SD大鼠，体重220～260g。48只大鼠随机分4组（12只／组），sham组：假手术＋生理盐水；SNL组：SNL＋生理盐水；M＋sham组：假手术＋米诺环素50μg；M＋SNL组：SNL＋米诺环素50μg；分别于术前及术后不同时点用von Frey纤维丝测定四组大鼠的机械撤爪阚值，并在机械痛阈最低点取脊髓腰膨大部进行Westernblot实验半定量检测四组中NMDAR1的表达。结果：SNL组与sham组比较大鼠术后各时点机械缩爪阂值明显下降，并在术后第8天降至最低点（P〈0．01）。M＋SNL组与SNL组比较，术后各时点大鼠机械撤爪阈值增高，脊髓NMDAR1的表达下降（P〈0．01）。结论：鞘内给予米诺环素可减轻SNL大鼠的机械痛敏，并抑制脊髓NMDAR1的表达。活化的小胶质细胞可能通过上调脊髓NMDAR1表达而参与了神经病理性疼痛的发生。Objective ： To investigate the effect of intrathecal minocycline on spinal NMDA receptor 1 subunit （ NMDAR1 ） expression in rat models of L5 spinal nerve ligation （SNL）. Methods ： Fourty eight male SD rats weighting 220 ~ 260 g were randomly divided into four groups （n = 12） ： sham group, sham operation ＋ 0.9% saline; SNL group, L5 spinal nerve ligation ＋ 0.9% saline; M ＋ sham group, sham operation ＋ minocycline 50 μg ; M ＋ SNL group, L5 spinal nerve ligation ＋ minocycline 50 μg. Mechanical withdrawal threshold was measured with yon Frey filagment at different timepoints in rats. Spinal NMDAR1 expression was detected by Western blot assay at the timepoint of the lowest withdrawal threshold. Results： Rats developed mechanical allodynia-like behavior after SNL and allodynia in the ipsilateral paw was fully expressed at 8th day after operation （ P 〈 0.01 ）. Intrathecal minocycline 50 μg reduced this allodynia significantly and decreased spinal expression of NMDAR1 in SNL rats compared with saline treatment （P 〈0.01 ）. Conclusion： Intrathecal administration of minocycline can attenuate allodynia induced by SNL, and activated microglia may upregulate the expression of NMDAR1 which contribute to the development of neurophathic pain.

关 键 词：神经病理性疼痛 小胶质细胞 米诺环素 NMDA受体 

分 类 号：R96[医药卫生—药理学]