神经痛大鼠脊髓胶质细胞源性神经营养因子参与多巴胺D2受体激动剂对痛觉过敏的调制作用

目的 研究鞘内注射多巴胺D2受体激动剂喹吡罗对坐骨神经慢性压迫损伤大鼠脊髓水平胶质细胞源性神经营养因子表达的影响,探讨其介导抗伤害作用的可能机制. 方法 实验1：采用完全随机分组方法将30只成年雄性SD大鼠制作坐骨神经慢性压迫损伤（chronic constriction injury of sciatic nerve,CCI）模型分为5组（每组6只）：CCI＋生理盐水（NS组）、CCI＋喹吡罗0.1 μg（Q0.1组）、CCI＋喹吡罗1μg（Q1组）、CCI＋喹吡罗5 μg（Q5组）、CCI＋喹吡罗10 μg（Q10组）,分别在建模后第7天鞘内注射0.1、1、5、10 μg喹吡罗,NS组单次鞘内注射生理盐水10μl.于给药前及给药后0.5、1、2、4、8、16h测定大鼠术侧后足机械缩足反射阈值（paw withdrawal mechanical threshold,PWMT）和热缩足反射潜伏期（paw withdrawal thermal latency,PWTL）.实验2：将54只成年雄性SD大鼠制作CCI模型,并采用完全随机分组方法分为3组（Q5组、Q10组、NS组,每组18只）：Q5组、Q10组分别在建模后第7天鞘内注射5、10μg喹吡罗后0.5、1、2、4、8、16h处死取材,NS组单次鞘内注射生理盐水10μl;另取6只正常大鼠作为模型对照组（M组）,另取6只正常大鼠作为对照组（C组）.采用免疫印迹法测定脊髓背角胶质细胞源性神经营养因子（glial cell line-derived neurotrophic fact,GDNF）蛋白表达的变化. 结果 实验1：与NS组比较,Q0.1组注药后各时间点PWMT和PWTL差异无统计学意义（P＞0.05）,Q1组注药后2 h PWMT[（4.3±1.5）g]及PWTL[（13.2±1.6）s],Q5组注药后1,2、4 h PWMT[（4.7±1.6）、（5.3±1.6）、（4.7±2.1）g]和PWTL[（14.0±1.7）、（15.2±1.5）、（13.4±1.6）s],Q10组注药后1、2、4 h PWMT[（6.0±1.3）、（7.3±1.0）、（5.3±2.1）g]和PWTL [（15.3±1.8）、（17.5±1.2）、（14.9±1.7）s]明显升高（P＜0.05）.实验2：与C组比较,M组GDNF表达（0.95±0.09）明显升高（P＜0.05）.与M组和NS组比较,GDNF的表达Q

Neurotrophic factor derived from spinal cord glial cell line in rats with neuropathic pain involved in the modulation of dopamine D2 receptor agonists hyperalgesia

Objective To study the effects of intrathecal injection of dopamine D2 receptor agonist quinpirole on expression of glial cell line-derived neurotrophic factor in the spinal cord in rats with chronic constrictive injury （CCI） and explore its possible mechanism of mediating antinociception.Methods In this study,models were established CCI in male Sprague-Dawley rats.The experiment was performed as 2 parts.In part one,30 CCI rats were randomly divided into 5 groups （n=6）：CCI＋saline （group NS）,CCI＋quinpirole 0.1 μg （group Q0.1）,CCI＋quinpirole 1 μg （group Q1）,CCI＋quinpirole 5 μg （group Q5）,CCI＋quinpirole 10μg （group Q 10）.The drugs were injected intrathecally on day 7 after CCI,respectively.Paw withdrawal mechanical threshold （PWMT） and paw withdrawal thermal latency （PWTL） were measured before and at 0.5,1,2,4,8 h and 16 h after intrathecal injection.In part two 54 CCI rats were randomly divided into 3 groups （group Q5,Q10 and NS,n=18）.Group Q5 and Q10 were sacrificed at 0.5,1,2,4,8,16 h after intrathecal quinpirole 5,10 μg on day 7 after CCI.Group NS,a single intrathecal injection of saline 10 μl.Group M,another 6 normal rats as model control group.Another 6 normal rats as control group C.The expression of glial cell linederived neurotrophic fact （GDNF） in the spinal cord was determined by Western blot.Results Part one：compared with group NS,the PWMT and PWTL of group Q0.1 at each time point after injection had no statistically significant difference （P〉0.05）.The PWMT and PWTL of 2 h of group Q1 [（4.3±1.5） g,（13.2±1.6） s].1,2,4 h of group Q5 [（4.7±1.6）,（5.3±1.6）,（4.7±2.1） g,（14.0±1.7）,（15.2±1.5）,（13.4±1.6） s] and Q10 [（6.0±1.3）,（7.3±1.0）,（5.3±2.1） g,（15.3±1.8）,（17.5±1.2）,（14.9±1.7） s] after drug administration were significantly promoted （P〈0.05）.Part two：compared with group C,the expression of GDNF was significantly increased in group M （0.95±0.09）（P〈0.05）.C