山龙眼属植物酚苷类化学成分豆腐果苷调控NGF/TrkA-TRPs通路发挥抗神经病理性疼痛作用机制研究

项目名称： 山龙眼属植物酚苷类化学成分豆腐果苷调控NGF/TrkA-TRPs通路发挥抗神经病理性疼痛作用机制研究

项目编号： No.81503236

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： 贾元威

作者单位： 皖南医学院

项目金额： 18万元

中文摘要： NGF/TrkA-TRPs通路是产生神经病理性疼痛的关键通路。山龙眼属植物中酚苷类化学成分豆腐果苷具有确切的抗神经病理性疼痛作用，但药效作用靶点及机制未明。申请者前期研究发现豆腐果苷的药效作用时程、组织分布特征、拮抗NGF诱导的神经细胞分化作用，均与NGF/TrkA-TRPs通路显示极大相关性。据此申请者提出科学假设：“豆腐果苷通过抑制NGF/TrkA-TRPs通路，减少TRPs的表达和活性，从而产生抗神经病理性疼痛作用”。申请者拟通过细胞水平研究明确豆腐果苷对NGF/TrkA-TRPs通路各环节的作用；整体水平考察豆腐果苷药效时程与NGF/TrkA-TRPs通路各环节时程变化的相关性；最后，构建豆腐果苷抗神经病理性疼痛作用PK-PD结合模型，进一步阐释其药理作用机制。上述研究将阐明豆腐果苷抗神经病理性疼痛机制，为同属植物酚苷类化学成分的活性研究提供借鉴，为新药设计与开发提供理论依据。

中文关键词： 神经源性疼痛；酚苷类；豆腐果苷；NGF/TrkA；TRPs；通道

英文摘要： NGF/TrkA-TRPs is the key pathway for neuropathic pain. Helicid, phenolic glycosides from Helicia Lour, produce exact curative effect on neuropathic pain. However, it is still unclear for the target and mechanism of the drug. Our previous study on helicid implied a correlation between its effects and NGF/TrkA-TRPs pathway: effect duration, tissue distribution characteristics, and its antagonistic effect to reverse the neural cell differentiation induced by NGF. Accordingly, the applicant proposes a scientific hypothesis: “Helicid inhibits NGF/TrkA-TRPs pathway, reduce expression and activity of TRPs, and result in its anti-neurogenic pain effect. Applicant will identify the effects of helicid on joints on NGF/TrkA -TRPs on cellular level. In vivo study will be conduct to indentify the correlations between the effect duration of helicid and changes in each element of NGF/TrkA-TRPs pathway. Finally, an anti-neuropathic pain PK-PD combined model for helicid will be established to further confirm the mechanism of helicid. The study will elucidate the anti-neuropathic pain mechanisms of helicid, provide a reference for activity study on phenolic glycosides from plants, and lay a theoretical basis for the design and development of new drugs.

英文关键词： neuropathic pain;phenolic glycoside;helicid;NGF/TrkA ;TRPs channel