鞘内注射氯胺酮对切口痛大鼠脊髓磷酸化p38丝裂原活化蛋白激酶和cAMP反应元件结合蛋白表达的影响

Influence of intrathecal ketamine injection on expression of spinal phosphorylated p38 mitogen-activated protein kinase and cAMP response element binding protein in rats with incision pain

目的观察鞘内注射氯胺酮对切口痛大鼠脊髓化p38丝裂原活化蛋白激酶（p38MAPK）和cAMP反应元件结合蛋白（pCREB）含量的影响。方法成年雄性Sprague-Dawley（SD）大鼠36只,体重250~300 g,随机分为3组：假手术组（Ⅰ组）,0.9%氯化钠溶液组（Ⅱ组,鞘内注射0.9%氯化钠溶液25μL）,氯胺酮组（Ⅲ组,鞘内注射100μg氯胺酮）。Ⅱ组、Ⅲ组均在切口痛术后立即给药,Ⅲ组鞘内给药用0.9%氯化钠溶液稀释至20μL,注射药物后再用0.9%氯化钠溶液5μL冲洗导管。采用von Frey丝测定术前1 h（T0）及术后2（T1）、4（T2）、8（T3）、16（T4）、24 h（T5）时大鼠后爪机械缩足阈值（PWT值）,随后在T5时间点取大鼠脊髓腰膨大部,采用Western印迹法测定磷酸化p38MAPK（p-p38MAPK）和CREB（pCREB）的表达。结果与Ⅱ组比较,Ⅰ组、Ⅲ组在术后各时间点（T1~T5时间点）的PWT值均显著升高（P值均〈0.05）。在T5时间点,与Ⅰ组比较,Ⅱ组大鼠脊髓p-p38MAPK和pCREB表达量均显著升高（P值均〈0.05）;与Ⅱ组比较,Ⅲ组大鼠脊髓p-p38MAPK和pCREB均显著降低（P值均〈0.05）。结论在大鼠切口痛模型中,鞘内注射氯胺酮可减轻大鼠急性切口痛,其镇痛作用可能是通过抑制p-p38MAPK/pCREB信号传导通路实现的。

Objective To observe the influence of intrathecal（IT） ketamine injection on the contents of spinal phosphorylated p38 mitogen-activated protein kinase（p38MAPK） and cyclic adenosine monophosphate（cAMP） response element binding protein（pCREB） in rats with incision pain.Methods Thirty-six adult male Sprague-Dawley rats were randomly divided into 3 groups： sham operation group（Group Ⅰ）,normal saline group（Group Ⅱ,IT 25 μL normal saline）,and ketamine group（Group Ⅲ,IT 100 μg ketamine dissolved 20 μL normal saline,and the catheter was flushed with 5 μL normal saline）.The paw-withdrawal threshold（PWT） was measured to assess the pain at T0-T5 time points after intrathecal injection by von Frey.The lumbar spinal cords of rats were taken out at T5 and the phosphorylated p38MAPK（p-p38MAPK） and CREB（pCREB） expression was examined by Western blotting analysis.Results Compared with groupⅡ,PWT values of groupⅠand Ⅲ increased at all time points（T0-T5） after incision（P0.05）.Compared with groupⅠ,expression of spinal phosphorylated p-p38MAPK and pCREB increased significantly in groupⅡ at T5（P0.05）;compared with groupⅡ,the expression of spinal phosphorylated p-p38MAPK and pCREB decreased in group Ⅲ at T5（P0.05）.Conclusion Intrathecal administration of katamine can reduce incision pain in rats with acute pain,which might be achieved by inhibiting phosphorylated p-p38MAPK/pCREB signal pathway.