Mrgprs基因的痒觉功能分析及天然致痒物的靶点筛选

项目名称： Mrgprs基因的痒觉功能分析及天然致痒物的靶点筛选

项目编号： No.31471007

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 神经、认识与心理学

项目作者： 唐宗湘

作者单位： 南京中医药大学

项目金额： 87万元

中文摘要： 天然产物中存在大量的致痒物质，但对它们的分子特性和作用靶点知道得很少。Mrgprs是一类新发现的由50多个成员组成的G蛋白偶联受体，并参与了外周痒觉的形成。前期研究结果表明MrgprA3、Mrgpr C11和MrgprD分别是氯喹、SLIGRL和β-alanine的分子靶点。最近我们从天然产物中得到了一种有效致痒成分NJUTCM-01，在诱导Mrgpr cluster △-/-和正常小鼠的痒觉行为存在显著差异，推测Mrgprs家族蛋白中存在NJUTCM-01的受体。本研究将采用行为学、钙成像、电生理、免疫组化、细胞培养和Mrgprs cDNA质粒表达等手段，确定NJUTCM-01的分子特性，筛选Mrgprs家族蛋白中NJUTCM-01作用的分子靶点，分析痒觉MrgprA3+神经元的生理特性及轴突末梢在脊髓和皮肤的分布模式，探索瘙痒形成的机制，寻找瘙痒治疗的新靶点和新途径。

中文关键词： Mrgprs基因；痒觉；致痒物质；靶点

英文摘要： A lot of pruritogenic substances exist in natural products, however their molecular targets are not well known. Mrgprs are newly identified G-protein-coupled receptors, whose family consists of more than 50 members, and participate in the formation of the peripheral itch. Previous researches have shown that MrgprA3, MrgprC11 and MrgprD are the molecular targets of Chloroquine, SLIGRL and β-alanine, respectively. Recently, we extracted a pruritogenic substance (NJUTCM-01) from natural products.There is signifincant difference when it was used to induce the scratching behavior between Mrgpr-cluster -/- and wilde type mice by a subcutaneous injection,and presume that there must be some receptors in Mrgprs to be associated with NJUTCM-01. This study will try to indentify the molecular properties of NJUTCM-01 which an effective component to induce itch was isolated and purified from natural product,screen the molecular targets of NJUTCM-01 in Mrgprs, analyze the physiological characteristics of MrgprA3+ neurons and their distribution patterns of axons terminal arbors projecting to spinal cord and skin,explore the mechanism of pruritus formation, seek the new targets and approaches for treating pruritus by employing the means of behavior, calcium imaging, electrophysiology,immunohistochemistry, cell culture and Mrgprs cDNA plasmids expression and so on.

英文关键词： Mrgprs genes;itch;pruritogenic substance;target