CD147在外周神经损伤病理性神经痛发生机制中的作用

项目名称： CD147在外周神经损伤病理性神经痛发生机制中的作用

项目编号： No.81471139

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： 吕岩

作者单位： 中国人民解放军第四军医大学

项目金额： 80万元

中文摘要： 基质金属蛋白酶（MMPs）通过细胞外基质蛋白的活化和裂解及促炎性细胞因子等的释放参与了多种神经退行性病变，并在伤害性感受和痛觉超敏中起着关键作用。CD147，细胞外基质金属蛋白酶诱导因子 (EMMPRIN)，可诱导MMPs的产生并与多种炎性相关疾病密切相关，但CD147与神经病理性疼痛的相关研究目前尚未见报道。基于预实验结果，我们提出假说：外周神经损伤后，背根神经节（DRG）细胞外基质中CD147表达上调，促进星形胶质细胞（卫星细胞）分泌 MMPs，通过炎性因子等诱导DRG神经元敏化，从而参与神经病理性疼痛的发生过程。本研究以CD147在外周神经损伤后的异常表达为突破口，探索外周神经损伤引起的神经病理性疼痛的相关机制，为寻找治疗神经病理性疼痛的有效药物提供理论依据和作用靶点。本研究亦可为提出神经病理性疼痛新机制假说，神经元 - 胶质细胞 - 细胞外基质的交互作用学说，提供初步的实验依据。

中文关键词： CD147；神经病理性疼痛；背根神经节；基质金属蛋白酶；细胞外基质

英文摘要： Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases through the cleavage of the extracellular matrix and enhancement of cytokines, chemokines, growth factors, cell surface receptors and cell adhesion molecules, and play an important role in nociception and allodynia. CD147, the extracellular MMP inducer (EMMPRIN), is an adhesion molecule, which has been known to play a key regulatory role for MMP activities. However, the role of CD147 in the development of neuropathic pain is not clear. Based on our preliminary experiments, we therefore proposed a hypothesis：after peripheral nerve injury, CD147 in the extracellular matrix of dorsal root ganglia (DRG) is upregulated, then increases the expression and secretion of MMPs in astrocyte (satellite cell) of DRG, and finally induces sensitization of DRG neurons through inflammatory factors. Therefore CD147 may contribute to the development of neuropathic pain. CD147, a key molecule in the extracellular matrix of DRG could be a new target for the treatment of neuropathic pain. The present project will utilize morphological, patch clamp and molecular biological techniques to examine the potential role of CD147 in the development of neuropathic pain. This study may also provide preliminary evidence for the proposal of a new hypothesis of neuropathic pain induced by nerve injury: the interaction between neuron, glia and extracellular matrix.

英文关键词： CD147;neuropathic pain;dorsal root ganglion;MMPs;extracellular matrix