神经病理性痛大鼠脊髓背角小胶质细胞及NMDAR1GABABR2的表达.DOCVIP

PAGE PAGE 1 作者单位：200233上海交通大学附属第六人民医院疼痛科 通讯作者：杜冬萍 神经病理性痛大鼠脊髓背角小胶质细胞和GABABR2的表达变化 浦少锋 吴军珍 杜冬萍 【摘要】目的 探讨小胶质细胞与γ-氨基丁酸B型受体2（GABABR2）在神经病理性疼痛中的作用及可能机制。方法 选择健康雄性SD大鼠48只随机分为4组：手术+鞘内注射生理盐水组(SN，n=12)，手术+鞘内注射米诺环素组(SM，n=12) ,假手术+鞘内注射生理盐水组（AN，n=12)，假手术+鞘内注射米诺环素组(AM，n=12)。SN及SM组大鼠结扎腰5神经根建立神经病理性疼痛模型（L5SNL),AN及AM组则暴露而不结扎腰5神经根。所有大鼠按组别每天2次鞘内注射米诺环素或生理盐水，通过测定大鼠各时点机械缩足反射痛阈（MWT）来评价大鼠机械痛敏，并在术后第8天通过免疫荧光方法测定大鼠脊髓背角小胶质细胞及背角神经元上GABABR2的表达情况。结果 SNL大鼠从术后1d即形成稳定的机械痛敏，术后8天机械缩足阈值降至最低。鞘内注射米诺环素可以提高SNL大鼠的MWT（P0.05)。免疫荧光显示，术后第8d， 手术组术侧脊髓背角GABABR2在术后第8天表达下降，鞘内注射米诺环素使GABABR2的表达下降程度减轻（P0.05)。结论 鞘内注射小胶质细胞特异抑制剂米诺环素可以明显抑制SNL大鼠的机械痛敏，并引起脊髓背角神经元上GABAR2的表达变化，表明小胶质细胞和GABABR2均参与了神经病理性疼痛的形成和发展，并提示GABABR2可能是作为小胶质细胞的下游机制参与了神经病理性疼痛的发生发展过程。 【关键词】神经病理性疼痛；GABABR2；小胶质细胞；免疫荧光 The effect and association of the spinal microglia and GABABR2 in the neuropathic pain. PU shaofeng，DU dongping，department of Pain Management Center，the Sixth People’s Hospital Afiliated to Shanghai Jiaotong University，Shanghai 200233 【Abstract]】Objectiv To explore the effect and association of the microglia and GABABR2 in the neuropathic pain .Methods fourty-eight mail SD adult rats were randomly divided into 4 groups: SNL +Minocycline group(SM,n=12),SNL+NS group(SN,n=12),SHAM Surgery+ Minocycline(AM,n=12), SHAM Surgery+ NS(AN,n=12).Neuropathic Pain model was created by L5 spinal nerve ligation(SNL).The rats were intrathecal injected with Minocycline or NS respectively according to the group. Mechanical withdrawal threshold was measured with von Frey filagment at different time points in rats. Spinal microglia and GABABR2 expression was detected by Immunohistochemistry at 8th day after Surgery. Result：Rats’ mechanical allodynia were formed at the first day after SNL and fully expressed at 8th day after operation(P0.01)．Intrathecal minocycline reduced this allodynia significantly （P0.05）and increased spinal expression of GABABR2 in SNL rats compared with saline treatment(P0.01).Conclusion Intrathecal administration of the microglia specific inhi