脊髓NO／cGMP信号通路在右美托咪定减轻大鼠神经病理性痛中的作用  

Role of NO/cGMP signaling pathway in dexmedetomidine-induced reduction of neuropathic pain in rats

作　　者：张碧玉[1] 颜学军[2] 王军[2] 

机构地区：[1]徐州医学院研究生学院江苏省麻醉学重点实验室,221004 [2]徐州医学院附属淮安医院麻醉科,223002

出　　处：《中华麻醉学杂志》2016年第4期481-483,共3页Chinese Journal of Anesthesiology

摘　　要：目的探讨脊髓一氧化氮/环磷酸鸟苷（NO/cGMP）信号通路在右美托咪定减轻大鼠神经病理性痛中的作用。 方法健康雄性SD大鼠42只，体重200～250 g，采用随机数字表法分为7组（n＝6）：正常对照组（C组）、神经病理性痛组（NP组）、右美托咪定组（D组）、二甲基亚砜组（DMSO组）、非选择性一氧化氮合酶抑制剂L-NAME组（L-NAME组）、L-NAME无活性对映异构（D-NAME）组（D-NAME组）和可溶性鸟苷酸环化酶抑制剂（ODQ）组（ODQ组）。采用坐骨神经慢性压迫（CCI）法制备神经病理性痛模型。于CCI后第7天，D组鞘内注射右美托咪定1.5 μg/kg；DMSO组、L-NAME组、D-NAME组和ODQ组分别鞘内注射二甲基亚砜10 μl、L-NAME 100 μg、D-NAME 100 μg和ODQ 10 μg，25 min后鞘内注射右美托咪定1.5 μg/kg。于鞘内给药即刻、给药后30、60、90、120、150、180和210 min时测定热缩足潜伏期，计算热缩足潜伏期曲线下面积以反映热痛阈水平。结果与C组比较，其余6组热痛阈降低（P〈0.05）；与NP组比较，D组、DMSO组、L-NAME组、ODQ组和D-NAME组热痛阈升高（P〈0.05）；与D组比较，L-NAME组和ODQ组热痛阈降低（P〈0.05），D-NAME组和DMSO组热痛阈差异无统计学意义（P〉0.05）。结论右美托咪定减轻大鼠神经病理性痛的机制与激活脊髓NO/cGMP信号通路有关。Objective To investigate the role of nitric oxide/cyclic guanosine monophosphate （NO/ cGMP） signaling pathway in dexmedetomidine-induced reduction of neuropathic pain （NP） in the rats. Methods Forty-two healthy male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into 7 groups （n= 6 each） using a random number table： normal control group （ C group） ; NP group; dexmedetomidine group （D group） ; dimethyl sulfoxide （DMSO） group; a non-selective nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester （L-NAME） group （L-NAME group） ; inactive enantiomer D-NAME group （ D-NAME group） ; a soluble guanylyl eyclase inhibitor 1H- [ 1,2,4 ] oxidazole [ 4,3-α ] qninoxalin- 1- one （ODQ） group （ ODQ group）. NP was induced by chronic constriction injury to the sciatic nerve in anesthetized rats. On day 7 after chronic constriction injury, dexmedetomidine 1.5 μg/kg was injected intrathecally in group D, and in DMSO, L-NAME, D-NAME and ODQ groups, DMSO 10 μl, L-NAME 100 μg, D-NAME 100μg and ODQ 10μg were injected intrathecally, respectively, and 25 min later dexmedetomidine 1.5 μg/kg was injected intratheeally. The thermal paw withdrawal latency was measured immediately after intrathecal administration and at 30, 60, 90, 120, 150, 180 and 210 min after intrathecal administration, and the area under the curve of thermal paw withdrawal latency was calculated to reflect the thermal pain threshold. Results Compared with group C, the thermal pain threshold was significantly decreased in the other six groups （P〈0.05）. The thermal pain threshold was significantly higher in D, DMSO, L-NAME, ODQ and D-NAME groups than in group NP （P〈0.05）. Compared with group D, the thermal pain threshold was significantly decreased in L-NAME and ODQ groups （P〈0.05） , and no significant change was found in the thermal pain threshold in D-NAME and DMSO groups （P〉0.05）. Conclusion The mechanism by which dexmedetomidine reduces NP is related to activation of NO

关 键 词：右美托咪啶 神经痛 一氧化氮 环GMP 脊髓 

分 类 号：R614[医药卫生—麻醉学]