基于TLR2信号通路的“针刺止痒”中枢神经传导机制研究

项目名称： 基于TLR2信号通路的“针刺止痒”中枢神经传导机制研究

项目编号： No.81503651

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 易伟民

作者单位： 中山大学

项目金额： 18万元

中文摘要： 瘙痒是常见的临床症状，严重的瘙痒给病患造成的痛苦程度并不亚于慢性疼痛。针刺治疗瘙痒具有良好疗效，但对于针刺止痒效应的中枢神经传导机制仍知之甚少。我们在前期研究中发现TLR2可能参与瘙痒的中枢神经传导，某些microRNA可能是TLR2信号通路的重要调控因子，而针刺可调节TLR2中枢水平表达，由此我们推测针刺止痒效应与TLR2有密切关系。我们采用针刺预处理曲池、血海，以吗啡诱导的野生型和TLR2基因敲除小鼠瘙痒模型作为研究切入点，在排除外周瘙痒病因作用和抑制疼痛神经传导情况下, 上调和下调TLR2信号通路，证实TLR2在针刺止痒中枢神经传导的作用；同时研究脊髓背角神经元水平的神经冲动及相关神经递质，使用microRNA芯片筛选，确定脑脊液和脊髓背角神经元中的差异microRNA并完成靶基因测试，有望明确针刺止痒神经传导过程中TLR2信号通路的调控机制，初步探索针刺整体效应的中枢神经传导机制。

中文关键词： 针刺研究；；瘙痒；TLR2；信号通路；中枢神经传导；脊髓水平

英文摘要： Pruritus is a common clinical symptom. Severe pruritus may cause malaise no less than chronic pain. Acupuncture treatment for pruritus has good effect, but the mechanism of acupuncture anti-pruritic effect is still poorly understood in central nervous conduction. In our previous study, we found that TLR2 might participate in the central nervous conduction of pruritus, and some microRNA might be important regulatory factors in the signal pathway of TLR2. Acupuncture could adjust TRL2 expression in central level according to literatures. Thus we speculate the anti-pruritic effect of acupuncture has close relationship with TLR2. We apply acupuncture preconditioning in the acupoints of LI11 and SP10. With wild type and TLR2 gene knockout mice models of morphine induced pruritus taken as a research pointcut, peripheral pruritic cause will be eliminated and nerve condution of pain will be suppressed. TRL2 signal pathway will be upregulated and downregulated in order to confirm TLR2 functions in acupuncture anti-pruritic effect in central nervous conduction. We will also study the nerve impulses in the level of spinal cord dorsal horn neurons and its related neurotransmitters. Furthermore, microRNA chip screening will be applied to determine the differential microRNA in cerebrospinal fluid and spinal cord dorsal horn neurons, and target gene test will be completed. The project will be expected to illuminate the regulating mechanism of TLR2 signal pathway in acupuncture anti-pruritic effect in the process of nervous conduction, and to preliminarily explore the mechanism of acupuncture part-whole effect in central nervous conduction.

英文关键词： Acupuncture research;Pruritus;Signal pathway of toll-like receptor 2;Central nervous conduction;Spinal cord level