米诺环素和TrkB/Fc对神经病理性疼痛发生期大鼠脊髓背角脑源性神经营养因子表达的影响  

Effects of minocycline and TrkB/Fc on spinal brain-derived neurotrophic factor expression during development of neuropathic pain in rats

作　　者：张昕[1,2] 吴军珍[1] 徐永明[1] 杜冬萍[1] 江伟[2] 

机构地区：[1]上海交通大学附属第六人民医院疼痛诊疗特色专科,200233 [2]上海交通大学附属第六人民医院麻醉科,200233

出　　处：《上海医学》2011年第4期257-260,共4页Shanghai Medical Journal

摘　　要：目的观察鞘内注射小胶质细胞抑制剂米诺环素、脑源性神经营养因子(BDNF)拮抗剂TrkB/Fc对大鼠神经病理性疼痛发生期脊髓背角BDNF表达的影响,探讨BDNF在神经病理性疼痛发生中的作用机制。方法成年雄性Sprague-Dawley(SD)大鼠42只,行鞘内置管,建立L5神经根结扎(SNL)致神经病理性疼痛模型,仅切开皮肤及皮下组织暴露L5神经根者为假手术。根据手术类型及注射药物的不同分为7组,每组6只:Ⅰ组,对照基础值组,鞘内置管成功大鼠,不用任何药物;Ⅱ组,鞘内注射1g/LTrkB/Fc10μL+SNL组,观察TrkB/Fc对SNL大鼠的作用;Ⅲ组,鞘内注射1g/LTrkB/Fc10μL+假手术组,观察TrkB/Fc对假手术大鼠的作用;Ⅳ组,鞘内注射磷酸盐缓冲液(PBS)10μL+SNL组,使用溶剂PBS作为对照组,观察溶剂对SNL大鼠的作用;Ⅴ组,鞘内注射PBS10μL+假手术组,观察溶剂对假手术大鼠的作用;Ⅵ组,鞘内注射8g/L米诺环素10μL+SNL组,观察米诺环素对SNL大鼠的作用;Ⅶ组,鞘内注射8g/L米诺环素10μL+假手术组,观察米诺环素对假手术大鼠的作用。分别于术前1h、末次给药前1h用vonFrey纤维丝以up-down法测大鼠的50%机械缩爪阈值(50%PWT)。末次给药后3h取手术侧腰膨大段脊髓背角,采用Western印迹法测定BDNF。结果末次给药前1h,Ⅳ组的50%PWT较术前1h明显降低(P<0.01),其余各组的差异均无统计学意义(P值均>0.05)。末次给药后3h,Ⅳ组术侧脊髓背角BDNF的表达显著高于其余各组(P值均<0.01),而其余各组间的差异均无统计学意义(P值均>0.05)。结论小胶质细胞抑制剂米诺环素、BDNF拮抗剂TrkB/Fc均能有效抑制神经病理性疼痛大鼠痛觉过敏的发生,疼痛发生期脊髓背角BDNF的表达增高可能与小胶质细胞的活化相关。Objective To investigate the effects of microglia cytostatic, minocycline, and brain-derived neurotrophic factor （BDNF） antagonist, TrkB/Fc on the expression of spinal BDNF during the development phase of neuropathic pain. Methods Forty-two male adult Sprague-Dawley （SD） rats weighting 200 to 260 g were intrathecally catheterized, and then assigned to left Lumbar 5 （L5） spinal nerve ligation （SNL） or sham operation. The rats were randomly divided into 7 groups （n=6 each）： groupⅠ basic control （only catheterized）; group Ⅱ TrkB/Fc （1 g/L, 10 μL）＋SNL; group Ⅲ TrkB/Fc ＋Sham; group Ⅳ PBS （10 μL）＋SNL; groupⅤ PBS＋Sham; group Ⅵ minocycline （8 g/L, 10 μL）＋SNL; and groupⅦ minocycline＋Sham. 50% Paw withdrawal threshold （50% PWT） to von Frey filament simulation was measured 1 h before operation and 1 h before the last injection. BDNF expression in the dorsal horn was detected by Western blotting analysis 3 h after the last injection. Results 50% PWT in group Ⅳ was decreased in 1 h before operation than in 1 h before the last injection （P〈0.01）, but there was no difference in other groups （P〉0.05）. In the group Ⅳ, the BDNF expression in the dorsal horn was significantly higher 3 h after last injection than that in other groups （P〈0.01）, but no difference was found among other groups （P〉0.05）. Conclusion Both minocycline and BDNF can prevent the development of neuropathic pain. The up-regulated BDNF during the development of neuropathic pain might be due to activation of microglial.

关 键 词：脑源性神经营养因子 神经痛 脊髓 小胶质细胞 米诺环素 TrkB/Fc 

分 类 号：R741[医药卫生—神经病学与精神病学]