摘要
建立坐骨神经慢性压迫损伤诱导的大鼠神经病理性疼痛模型(CCI模型),探讨左旋紫堇达明(levo-corydalmine,l-CDL)对神经病理性疼痛大鼠痛觉敏化和脊髓中枢敏化的影响。Von-frey法检测机械性缩足反射阈值;热痛刺激仪检测热刺激缩足反射潜伏期;免疫印迹法检测大鼠脊髓L4-L6段N-甲基-D-天冬氨酸受体NR1亚基磷酸化水平;免疫荧光法检测脊髓背角降钙素基因相关肽(CGRP)蛋白表达以及c-fos阳性神经元数目。结果显示,l-CDL(7.5,15 30 mg/kg,ig)能够剂量依赖性地改善CCI模型大鼠机械超敏和热痛过敏。l-CDL[15 mg/(kg·d),5 d,ig]能显著抑制CCI模型大鼠脊髓CGRP,p-NR1,c-fos的高表达,且不发生镇痛耐受现象。表明l-CDL对CCI模型大鼠神经病理性疼痛具有良好的镇痛作用,其镇痛机制与抑制大鼠脊髓中枢敏化相关。
The aim of the present study was to investigate the effects of levo-corydalmine( l-CDL) on chronic constrictive injury( CCI)-induced neuropathic pain and central sensitization in spinal cord.The mechanical withdrawal threshold in rats was assessed by Von-Frey fibers and the thermal withdrawal latency was assessed by thermal stimulus apparatus.The level of phosphorylated N-methyl-D-aspartic acid receptor 1( NR1) in L4-L6 spinal cord was analyzed by immunoblotting and the expression of calcitonin gene related peptide( CGRP) and c-fos in spinal cord dorsal horn were analyzed by immunofluorescence.Results showed that l-CDL( 7.5,15,30 mg/kg,ig)inhibited CCI-induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner.l-CDL significantly inhibited the up-regulation of p-NR1,c-fos and CGRP in CCI rats without tolerance.In conclusion,l-CDL has a good relieving effect on central sensitization in spinal cord,thus generating outstanding analgesic activity on CCI-induced neuropathic pain.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2017年第1期70-75,共6页
Journal of China Pharmaceutical University
基金
国家"重大新药创制"科技重大专项资助项目(No.2012ZX09J12110-06B)~~