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青藤碱对SSNI模型大鼠镇痛效应及脑内兴奋性氨基酸递质的影响
引用本文:李鹏,张美玉,王丹巧,徐奭,徐晓军.青藤碱对SSNI模型大鼠镇痛效应及脑内兴奋性氨基酸递质的影响[J].中国药理学通报,2012(10):1365-1369.
作者姓名:李鹏  张美玉  王丹巧  徐奭  徐晓军
作者单位:1. 中国中医科学院医学实验中心,北京100700
2. 首都师范大学生命科学学院,北京 100048
3. 卡罗林斯卡医学院,斯德哥尔摩瑞典 14186
基金项目:国家科学技术部国际科技合作项目(No 2010DFA31890)
摘    要:目的观察青藤碱对部分坐骨神经损伤(SSNI)模型大鼠疼痛敏感行为及纹状体细胞外液兴奋性氨基酸-谷氨酸(Glu)的影响。方法 SD大鼠,随机分为假手术组和SSNI手术组,后者再分为模型组、加巴喷丁组(100 mg.kg-1)、青藤碱低剂量组(20 mg.kg-1)和青藤碱高剂量组(40 mg.kg-1)。采用机械痛敏和冷痛敏测试,评价大鼠的疼痛行为,以最大镇痛效应百分比(%MPE)反映药效。纹状体微透析采样,高效液相-荧光方法检测其细胞外液Glu浓度。结果 SSNI模型大鼠的机械、冷刺激痛感行为明显改变,脑内Glu水平明显升高。%MPE效应-时间曲线在120min内青藤碱高剂量组最高(达81.28%),加巴喷丁组第2(达50.56%),青藤碱低剂量组第3(达7.22%)。与模型组纹状体细胞外液Glu水平相比,加巴喷丁组有3个时间点、青藤碱低剂量组有4个时间点、青藤碱高剂量组有5个时间点明显降低(P<0.05或P<0.01)。结论青藤碱减轻SSNI模型大鼠疼痛敏感行为,其镇痛效应可能与抑制纹状体细胞外液Glu水平有关。

关 键 词:青藤碱  部分坐骨神经损伤  脑内微透析  谷氨酸  机械痛敏  冷痛敏

Effects of sinomenine on analgesia and exciting amino acid neurotransmitters in brain of SSNI rat model
LI Peng,ZHANG Mei-yu,WANG Dan-qiao,XU Shi,XU Xiao-jun.Effects of sinomenine on analgesia and exciting amino acid neurotransmitters in brain of SSNI rat model[J].Chinese Pharmacological Bulletin,2012(10):1365-1369.
Authors:LI Peng  ZHANG Mei-yu  WANG Dan-qiao  XU Shi  XU Xiao-jun
Institution:1.Experimental Research Centre,China Academy of Traditional Chinese Medicine,Beijing 100700,China;2.College of Life Sciences,Capital Normal University,Beijing 100048,China;3.Karolinska Hospital-Huddinge,Stockholm 14186,Sweden)
Abstract:Aim To investigate the effects of sinomenine on pain sensitive behavior and extracellular exciting amino acid-glutamate(GLU) in striatum of spared sciatic nerve injury(SSNI) rat model.Methods Sprague-Dawley rats were randomly divided into sham operation group and SSNI surgical group.The latter group was further separated into model group,gabapentin group(100 mg.kg-1),sinomenine low-dose group(20 mg.kg-1) and sinomenine high-dose group(40 mg.kg-1).The tests of mechanical allodynia and cold allodynia were used to evaluate the pain behavior of the rats and the analgesia efficacy of the drugs were calculated by the percentage of maximal possible effect(%MPE).The samples were collected from striatum by microdialysis technique and the extracelluar GLU concentration of the samples were measured by high performance liquid chromatography-fluorescence detector(HPLC-FLD).Results The mechanical and cold pain sensitive behaviors of SSNI rats changed significantly and the GLU level in the brain of these rats increased significantly,too.Within 120 minutes,sinomenine high-dose group had the highest % MPE effecttime curve(81.28%),with gabapentin group in the middle(50.56%) and sinomenine low-dose group as the lowest(7.22%).Compared with the extracellular GLU level in striatum of model group,3 time points in gabapentin group,4 time points in sinomenine lowdose group,and 5 time points in sinomenine high-dose group were decreased significantly(P < 0.05 or P < 0.01).Conclusions Sinomenine can relieve the pain sensitive behavior of SSNI rats.Its analgesic effect may be related to inhibiting extracellular GLU level in striatum.
Keywords:sinomenine  spared sciatic nerve injury  brain microdialysis  glutamate  mechanical hyperalgesia  cold hyperalgesia
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