鞘内注射GABA转运体-1抑制剂NO-711对神经病理痛大鼠脊髓Fos蛋白表达的影响  

Effect of intrathecal NO-711 injection on expression of Fos protein after chronic constriction injury of the sciatic nerve in rats

作　　者：李轶聪[1] 付宝军[1] 刘芳[1] 李悦[2] 

机构地区：[1]解放军第211医院麻醉科,哈尔滨150080 [2]哈尔滨医科大学附属一院麻醉科,哈尔滨150001

出　　处：《中国新药杂志》2011年第12期1112-1116,共5页Chinese Journal of New Drugs

基　　金：黑龙江省自然基金课题(D200857)

摘　　要：目的:观察脊髓水平GABA转运体-1(γ-aminobutyric acid transporter-1,GAT-1)抑制剂NO-711对坐骨神经慢性松结扎(chronic constriction injury,CCI)大鼠机械痛敏和热痛敏以及Fos蛋白表达的影响,探讨NO-711抗伤害性的可能机制。方法:雄性SD大鼠84只,随机分为4组(n=21):假手术生理盐水组、假手术抑制剂组、神经损伤生理盐水组和神经损伤抑制剂组。各组大鼠CCI前5 d进行鞘内置管,在术前测定基础机械性缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足潜伏期(thermal withdrawal laten-cy,TWL)及Fos蛋白的表达,CCI后5 d鞘内注射100μg NO-711或生理盐水,测定节扎前、给药前、给药后0.5,1,2,4和8 h大鼠MWL和TWL及Fos蛋白的表达。结果:与给药前和神经损伤生理盐水组相比,神经损伤抑制剂组大鼠在给药后机械痛敏和热痛敏以及Fos蛋白的表达均逐渐降低,并随时间的延长又逐渐恢复到给药前水平,在给药后1 h时作用最明显,并一直持续到给药后4 h。结论:鞘内注射NO-711可通过抑制Fos蛋白表达明显减轻CCI大鼠机械痛敏和热痛敏。Objective： To observe the effect of the GAT-1 inhibitor NO-711 on behavior and c-fos expression in the dorsal horn of spinal cord after chronic constrictive injury（CCI） in rats,and to investigate the possible mechanism underlying its antinociceptive effect.Methods： Eighty four male Sprague-Dawley rats weighting 280~300 g were randomly divided into 4 groups（n=21 for each goup）.All the rats were intrathecally cathetered at 5 d before sciatic nerve ligation,on the 5th day after the ligation,and NO-711or NS was injected through the intrathecal catheter.Thermal withdrawal latency（TWL） and mechanical withdrawal threshold（MWT） of rats were determined by thermal radiation apparatus and von Frey microfilament before administration and 0.5,1,2,4 and 8 h after administration,respectively.The time course of c-fos expression was assessed by immunohistochemical analysis.Results： Intrathecal administration of NO-711 significantly attenuated the activation of c-fos induced by CCI,and simultaneously ameliorated mechanical and thermal hyperalgesia induced by CCI.The effect was the strongest at 1 h,lasted over 4 h,and returned to baseline value at 8 h after administration.Conclusion： Intrathecal NO-711 injection can attenuate the mechanical and heat hyperalgesia in CCI rats through inhibition of c-fos expression in the dorsal horn of spinal cord.

关 键 词：神经病理性痛 脊髓 FOS蛋白 GABA转运体-1(GAT-1)抑制剂 

分 类 号：R971[医药卫生—药品]