文章摘要
何庆标,闵宇懿,张绍杰,莫 力,王育明.nNOS磷酸化在大鼠神经病理性疼痛发病中的作用及其机制[J].南京医科大学学报,2016,(3):302~306
nNOS磷酸化在大鼠神经病理性疼痛发病中的作用及其机制
The mechanism of nNOS phosphorylation in spinal cord of neuropathic pain in rat
投稿时间:2015-10-22  
DOI:10.7655/NYDXBNS20160310
中文关键词: nNOS  CAPON  磷酸化  神经病理性疼痛
英文关键词: nNOS  CAPON  phosphorylation  neuropathic pain
基金项目:
作者单位
何庆标 武警广东省总队医院麻醉科,广东 广州 510507 
闵宇懿 南方医科大学南方医院儿科,广东 广州 510515 
张绍杰 武警广东省总队医院麻醉科,广东 广州 510507 
莫 力 武警广东省总队医院麻醉科,广东 广州 510507 
王育明 武警广东省总队医院麻醉科,广东 广州 510507 
摘要点击次数: 687
全文下载次数: 375
中文摘要:
      目的:探索神经结扎(spinal nerve ligation,SNL)模型大鼠脊髓内神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)的磷酸化是否对神经病理性疼痛具有调节作用,研究nNOS磷酸化在神经病理性疼痛中的作用机制。方法:选用雄性SPF级SD大鼠60只,随机分为4组。假手术组:只暴露脊神经,不结扎;实验组:制作SNL模型,鞘内注射钙依赖性蛋白激酶Ⅱ(phosphorylated calcium/calmodulin dependent kinaseⅡ,p-CaMKⅡ)抑制剂KN93;阴性对照组:制作SNL模型,鞘内注射DMSO;模型组:制作SNL模型,不给药。于术前1 d?术后1~5 d以及鞘内给药后1~4 h测定机械痛阈值。采用Western blot检测腰段脊髓组织p-CaMKⅡ?nNOS与p-nNOS的表达水平,利用免疫共沉淀以及免疫荧光实验检测nNOS与其接头蛋白CAPON是否具有相互作用。结果:SNL可导致大鼠机械疼痛阈值降低(P < 0.01),脊髓组织p-CaMKⅡ的表达增加(P < 0.05),p-nNOS的表达下降(P < 0.05),髓鞘内注射KN93可反转神经结扎所致的上述趋势;nNOS与其接头蛋白CAPON在大鼠体内存在相互作用,nNOS的磷酸化能降低其与CAPON的相互作用强度。结论:nNOS的磷酸化参与了SNL诱导的神经病理性疼痛的维持,p-CaMKⅡ通过对nNOS的磷酸化,降低nNOS与其接头蛋白CAPON在体内的相互作用强度,针对nNOS的磷酸化信号途径的治疗可为神经病理性疼痛的治疗提供新的视野。
英文摘要:
      Objective:To explore the effect of phosphorylation of neuronal nitric oxide synthase (nNOS) on regulation the neuropathic pain in spinal nerve ligation (SNL) model rats,and research the mechanism of nNOS phosphorylation in neuropathic pain. Methods:A total of 60 male SPF SD rats were randomly divided into 4 groups:the control group,only expose spinal nerve,not ligation;the experimental group,SNL model,KN93 (calcium/calmodulin dependent kinase Ⅱ inhibitor) intrathecal injection;the negative control group,SNL model,DMSO intrathecal injection;the model group,SNL model,didn′t receive any medicine. We determined mechanical pain threshold 1 day before operation,postoperative 1-5 days and 1-4 hours after sheath dosing. Western blot was performed to detect the expression level of calcium/calmodulin dependent kinase Ⅱ (p-CaMKⅡ),nNOS and pnNOS in lumbar spinal cord tissue. CoIP and immunofluorescence experiments was performed to test whether there was an interaction between nNOS and CAPON. Results:SNL led to mechanical pain threshold of rats reduced (P < 0.01),the expression of spinal cord tissue p-CaMKⅡincreased (P < 0.05),and the expression of p-nNOS decreased(P < 0.05). KN93 intrathecal injection reversed the trend above. There was an interaction between nNOS and CAPON,and the phosphorylation of nNOS reduced the strength of interaction between nNOS and CAPON. Conclusion:The phosphorylation of nNOS is involved in neuropathic pain induced by SNL,and p-CaMKⅡ make nNOS phosphorylation,reduced the strength of interaction between nNOS and CAPON. The nNOS signaling pathways can provide a new field of vision for neuropathy pain treatment.
查看全文   查看/发表评论  下载PDF阅读器
关闭