树突膜特异性表达的syndecan-2通过调节actin细胞骨架聚集参与神经病理性痛的机制研究

项目名称： 树突膜特异性表达的syndecan-2通过调节actin细胞骨架聚集参与神经病理性痛的机制研究

项目编号： No.81671084

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 刘岳鹏

作者单位： 南京医科大学

项目金额： 25万元

中文摘要： 新树突棘的发生，其膜上受体的数量增多、功能的活跃以及其中信号通路的活化导致中枢敏化和神经病理性痛，而细胞骨架actin在以上过程中都发挥一定的作用。Syndecan-2（SDC2）特异性地分布在树突膜上，具有调节actin的作用，可与EphB等受体协同。我们提出假说，SDC2分子在EphB和其调节酶heparanase 的作用下通过调节树突棘的actin而参与突触重塑和神经病理性痛。本课题首先以siRNA或shRNA特异性抑制SDC2的表达并观察其对慢性神经结扎引起的诱发痛和自发痛的影响以及对neurofibromin-cAMP-PKA-Ena/VASP-F-actin信号通路的影响，藉此来探讨SDC2调控疼痛的作用；其次干预heparanase和/或EphB并观察SDC2的表达来探讨两者与SDC2的关系。干扰SDC2可以“釜底抽薪”的策略精准地治疗神经病理性痛，是个潜在的优良的治疗靶点。

中文关键词： 多配体蛋白聚糖-2；神经病理性痛；细胞骨架；环磷腺苷；树突棘

英文摘要： The production of dendritic spines, increasing number and up-regulated function of receptors on its membrane, as well as the activation of its internal signal pathways, all lead to central sensitization and neuropathic pain, while the actin cytoskeleton plays a certain role in all the processes above mentioned. Syndecan-2 (SDC2) is distributed on the membrane of dendritic spines with specificity, and can regulate actin and play a synergistic role with receptors such as EphB. We then proposed the hypothesis that under the modulation of EphB and heparanase(regulatory enzyme of SDC2), SDC2 could participate in the remodeling of the synapse and neuropathic pain by regulating the actin of dendritic spines. In this study, first, when the expression of SDC2 was specifically inhibited by its siRNA or shRNA, its impacts on spontaneous pain and induced pain in chronic nerve ligation model and on expression of the SDC2-neurofibromin-cAMP-PKA-Ena/VASP-F-actin signal pathway were observed to investigate the regulatory role of SDC2 on kinds of pain; second, with drug intervention on heparanase and/ or EphB, the expression of SDC2 was observed to learn the relationship between heparanase/EphB and SDC2. The interference of SDC2 could precisely treat neuropathic pain as a drastic measure, so SDC2 was believe to be a potential therapeutic target for neuropathic pain.

英文关键词： syndecan-2;neuropathic pain ;cytoskeleton;cAMP;dendtritic spine