脊髓和海马突触长时程增强及PKMζ在慢性功能性内脏痛中枢敏化中的作用

项目名称： 脊髓和海马突触长时程增强及PKMζ在慢性功能性内脏痛中枢敏化中的作用

项目编号： No.81471138

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 林春

作者单位： 福建医科大学

项目金额： 75万元

中文摘要： 先前研究表明脊髓和海马中枢敏化均参与慢性内脏痛的形成。最近研究提示：突触长时程增强(LTP)可能在中枢敏化中起重要作用，而且PKMζ可能是LTP维持的关键效应分子。据此我们假设,脊髓和海马LTP通过PKMζ介导的信号通路在慢性功能性内脏痛中枢敏化中发挥重要作用。因此本项目拟采用慢性功能性内脏痛模型大鼠，以脊髓和海马为切入点，应用电生理、药理、分子生物学、行为学等相关技术手段，在前期研究的基础上，首先进一步明确突触LTP在慢性功能性内脏痛中枢敏化中的作用；其次求证PKMζ是否为LTP维持的关键效应分子；最后探讨PKMζ参与慢性内脏痛LTP维持的可能机制，以期揭示LTP在慢性内脏痛中枢敏化中的作用及其机制。结果不仅有助于进一步阐明慢性功能性内脏痛的发病机制，而且有望拓展该病的防治思路，为其治疗药物研发提供新的靶点。因此，开展本项目研究不仅具有重要的理论意义和科学价值，而且具有潜在的应用前景。

中文关键词： 蛋白激酶M；zeta；长时程增强；慢性内脏痛；中枢敏化；分子机制

英文摘要： Early studies demonstrated that spinal and hippocampal central sensitization were implicated with formation of chronic visceral pain. Recent studies indicated that long-term potentiation ( LTP ), as a cellular model for synaptic plasticity, is proposed as an important mechanism underlying central sensitization，and protein kinase M ζ (PKMζ) may contribute to the LTP maintaining. Therefore, we hypothesize that spinal and hippocampal LTP play important roles by PKMζ mediated signaling pathways in chronic visceral hypersensitivity. In this project, rats with chronic functional visceral pain were chosen as research objects, and the spinal cord and the hippocampus as pointcuts. On the basis of preliminary work, using method of electrophysiology, pharmacology, molecular biology, behavioristics and so on, first, we are going to further confirm that spinal and hippocampal LTP play important roles in chronic visceral hypersensitivity. Secondly, we will prove to effects of PKM ζ on LTP in chronic visceral hypersensitivity. At last, PKMζ mediated signaling pathways in LTP will be studied in order to clear the mechanism of LTP in central sensitization of chronic functional visceral pain. This study is original and essential for clearing the pathogenesis of chronic functional visceral pain, which may provide a new target for the treatment. Therefore, this project has not only important theoretical significance but also scientific value, and it has potential application prospect.

英文关键词： protein kinase Mζ;long-term potentiation;chronic visceral pain;central sensitization;molecular mechanism