米诺环素、氟代柠檬酸和B型酪氨酸激酶受体/Fc对维持期神经病理性疼痛大鼠脊髓背角脑源性神经营养因子表达的影响  

Inhibitory effect of minocycline,fluorocitrate and tyrosine kinase receptor B/Fc against expression of spinal brain-derived neurotrophic factor during maintenance phase of neuropathic pain

作　　者：徐永明[1] 张昕[1] 浦少锋[1] 吴军珍[1] 杜冬萍[1] 

机构地区：[1]上海交通大学附属第六人民医院疼痛科,200233

出　　处：《上海医学》2011年第6期414-417,共4页Shanghai Medical Journal

摘　　要：目的研究鞘内注射小胶质细胞抑制剂米诺环素、星形胶质细胞抑制剂氟代柠檬酸及脑源性神经营养因子(BDNF)清除剂B型酪氨酸激酶受体(TrkB)/Fc对神经病理性疼痛维持期大鼠的脊髓背角BDNF表达的影响,探讨BDNF在神经病理性疼痛维持期中的作用。方法取36只成功鞘内置管大鼠,随机分为6组,每组6只:Ⅰ组为对照组,未行神经根结扎(SNL)术,未给药;Ⅱ组为SNL组;Ⅲ组为SNL+磷酸盐缓冲液组;Ⅳ组为SNL+米诺环素组;Ⅴ组为SNL+氟代柠檬酸组;Ⅵ组为SNL+TrkB/Fc组。各组均于SNL术后7 d鞘内给药,每日1次,连续5 d。分别于SNL术前1 h、首次给药前1 h及末次给药前1 h测定大鼠的50%机械缩爪阈值(50%PWT),并于末次给药后3 h采用Western印迹法测定手术同侧脊髓背角的BDNF表达水平。结果除Ⅰ组外,其他各组大鼠在SNL术后第7天的50%PWT均较术前1 h显著降低(P值均<0.01)。连续用药5 d后,Ⅴ、Ⅵ组的50%PWT均较术后第7天显著升高(P值均<0.01)。Ⅱ、Ⅲ、Ⅳ组维持期给药后脊髓背角BDNF表达水平显著高于Ⅰ组(P值均<0.01),Ⅴ、Ⅵ组显著低于Ⅱ组(P值均<0.01)。结论星形胶质细胞抑制剂氟代柠檬酸能显著抑制神经病理性疼痛维持期大鼠脊髓背角BDNF的过表达,进而缓解神经病理性疼痛,而小胶质细胞抑制剂米诺环素对维持期神经病理性疼痛大鼠的作用甚小。BDNF对神经病理性疼痛大鼠机械痛觉过敏的维持起重要作用,其机制可能与星形胶质细胞的活化有关。Objective To investigate the effects of intrathecal injection of minocycline,fluorocitrate and tyrosine kinase receptor（Trk）B/Fc on expression of spinal brain-derived neurotrophic factor（BDNF） in rat dorsal horn during maintenance phase of neuropathic pain,so as to evaluate the role of BDNF in the maintenance of neuropathic pain.Methods Thirty six male Sprague-Dawley（SD） rats,weighing 200-260 g,were used in this study.After interthecal catheterization and left L5 spinal nerve ligation（SNL）,animals were randomly divided into 6 groups（n=6 each）： group Ⅰ control,group Ⅱ SNL,group Ⅲ SNL＋PBS,group Ⅳ SNL＋minocycline,group Ⅴ SNL＋fluorocitrate,and group Ⅵ SNL＋TrkB/Fc.Seven days after SNL,rats were given spinal administration of corresponding drugs once daily for 5 days;the 50% paw withdrawal threshold（PWT） was measured at different time points,and the BDNF expression in dorsal horn was detected by Western blotting analysis 3 h after last treatment.Results Seven days after SNL,50% PWT was lower than the baseline in all groups but group I at 7 days after SNL（all P0.01）.After intrathecal administration of corresponding drugs for 5 days,the 50% PWT increased only in TrkB/Fc and fluorocitrate groups compared with those at 7 days after operation（all P0.01）;and the dorsal horn BDNF expression in Ⅱ,Ⅲ,and Ⅳ groups was significantly higher than that in group Ⅰ（all P0.01）,and that in Ⅴ and Ⅵ group was significantly lower than that in the group Ⅱ（all P0.01）.Conclusion Fluorocitrate,not minocycline,can inhibit the up-regulation of BDNF induced by astrocytic activation in the maintenance of neuropathic pain.BDNF might play an important role in the maintenance of neuropathic pain,and the dorsal horn BDNF over-expression may be related to the astrocytic activation.

关 键 词：脑源性神经营养因子 神经病理性疼痛 米诺环素 氟代柠檬酸 

分 类 号：R965[医药卫生—药理学]