【摘要】 目的:观察蛛网膜下腔注射重组质粒pcDNA3.1(+)-hPPE对大鼠神经痛的镇痛作用。方法:SD大鼠随机分为坐骨神经慢性压迫(CCI)组、CCI假手术组、实验组和空质粒组。CCI组和CCI假手术组,用于观察疼痛持续时间;实验组和空质粒组分别于CCI术后第15天蛛网膜下腔注射重组质粒pcDNA3.1(+)-hPPE和空质粒pcDNA3.1(+)。测定各组注射质粒前后CCI模型鼠双后肢热痛阈(PWTL),观察纳洛酮对镇痛效应的影响,用放射免疫法检测脑脊液灌流液中脑啡肽(L-ENK)的含量,同时采用免疫组织化学方法测定两组大鼠脊髓背角N-甲基-D-天冬氨酸(NMDA)受体2B亚基(NR2B)表达的变化。结果:CCI术后7～33d,术侧PWTL明显低于对照侧。空质粒组注射前后热痛阈未见明显变化;与空质粒组相比,实验组大鼠蛛网膜下腔注射重组质粒pcDNA3.1(+)-hPPE后的第3天产生明显的抗伤害效应(PTWL升高),持续镇痛长达18d,且镇痛效应能被纳洛酮翻转。实验组脑脊液灌流液L-ENK含量显著高于空质粒组。与空质粒组比较,实验组大鼠脊髓背角NR2B阳性蛋白表达明显受到抑制。结论:蛛网膜下腔注射重组质粒pcDNA3.1(+)-hPPE能够减轻大鼠神经病理性疼痛的热痛敏行为。更多还原

【Abstract】 Objective:To observe the analgesic effect of intrathecal injection of pcDNA3.1(+)-hPPE recombinant plasmid on neuropathic pain in rats.Methods:Sprague-Dawley rats were randomly divided into four groups:chronic constriction injury of the sciatic nerve(CCI)group,sham-operated group,pcDNA3.1(+)-hPPE group and pcDNA3.1(+)group.The CCI group and the sham-operated group were designed for the observation of pain behavior duration.The pcDNA3.1(+)-hPPE recombinant plasmid and the eukaryotic expression vector pcDNA3.1(+)was intrathecally injected at a dose of 30μg/100μ1 at day 15 after CCI operation in the two groups.The paw withdrawal thermal latency(PWTL)was examinated before and after CCI operation.The effect of naloxone was tested;the concentrations of enkephalin in cerebrospinal perfusion fluid were measured with radioimmunoassay and the changes in NR2B protein expression in the spinal cord dorsal horn was detected with immunohistochemical techniques in both groups at day 18 after intrathecal injection.Results:7-33days after CCI,PWTL was significantly lower than that of the contralateral sides.There was no significant difference in PWTL in the pcDNA3.1(+)group after intrathecal injection at any test time;The right PTWL was significantly higher than that of the left PTWL in the pcDNA3.1(+)-hPPE group from 2 to 18days after intrathecal injection.The attenuation of the thermal hyperalgesia induced by CCI in the rats could be blocked by naloxone.The concentrations of the leucine enkephalin in CSF of the pcDNA3.1(+)-hPPE group were significantly higher than those in CSF of the pcDNA3.1(+)group.The expression of NR2B protein was significantly decreased in the spinal cord dorsal horn in the pcDNA3.1(+)-hPPE group.Conclusion:The pcDNA3.1(+)-hPPE recombinant plasmid transfecting into the subarachnoid space of CCI model rats via intrathecal injection may significantly attenuate thermal hyperalgesia.更多还原