赤霉素干扰GH-IGF-1轴及其相关信号转导通路的分子机制研究

项目名称： 赤霉素干扰GH-IGF-1轴及其相关信号转导通路的分子机制研究

项目编号： No.81473005

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： 钟才高

作者单位： 中南大学

项目金额： 70万元

中文摘要： 赤霉素（Gibberellin）俗称920，是目前现代农业生产应用范围最广的一种植物生长调节剂，国内外资料表明赤霉素对动物生长发育及肿瘤发生具有明显的促进作用，但其作用机制尚未阐明。本课题拟采用体内与体外试验相结合的方法探讨赤霉素对大鼠GH-IGF-1轴及其相关细胞信号转导通路的影响，阐明赤霉素促进动物生长发育的分子作用机制。其内容包括赤霉素对动物生长激素（GH）、肝细胞IGF-1、IGF-BP、IGF-1R、GHR活性及JAK/STAT、RAS/MAPK、PI3K/AKT等信号传导通路的影响。赤霉素已成为人类环境中的一种较为典型的环境类激素污染物，对人类健康具有严重的潜在性危害。本课题的意义在于通过探讨赤霉素干扰GH-IGF-1轴及细胞JAK/STAT等细胞信号转导通路的分子作用机制，为寻找监测赤霉素潜在性健康危害的敏感生物标记以及制定我国食品与饮水中赤霉素安全限值提供科学依据。

中文关键词： 赤霉素；生长激素；胰岛素样因子-1；信号转导通路；植物生长调节剂

英文摘要： Gibberellin,often also called as 920,is one of the most common plant growth regulators,which is widely used in modern agriculture with tremendous consumption and range of application at prensent. The domestic and foreign investigations have shown that gibberellin has obvious effect on promoting the growth and development of animals and tumorigenesis, however, the menchanism of action is not yet elucidated. In order to clarify the molecular mechanisms of gibberellin promoting the growth and development of animals, the methods of combining in vivo and in vitro will be adopted to investigate the molecular mechanisms on the effect of gibberellin on the GH-IGF-1 axis of rats and their related signal trasduction pathway of hepatocytes. The study will focus on the effects of gibberellin on animal growth hormone(GH) and growth hormone receptor(GHR),IGF-1,IGF-BP,IGF-1R biological activities and JAK/STAT RAS/MAPK,PI3K/AKT signal trasduction pathways in hepatocyte, etc. Gibberellin has become a common chemical pollutant in ecological environment of modern agriculture, which is a pretty typical environmental endocrine disrupting chemical, possessing serious potential hazards for human health. By exploring the molecular mechanisms that involved in Gibberellin-induced interference of GH-IGF-1 axis and JAK/STAT signaling, we will try to find the sensitive biomarkers that representing the potential harmful effect of Gibberellin, which will provide experimental evidences to formulate the safety limits of Gibberellin in the food and drinking water in China.

英文关键词： gibberellin;growth hormone;insulin-like growth factor-1;signal tranduction pathway;plant growth regulator