牛磺鹅去氧胆酸对大鼠肺泡巨噬细胞中TGR5受体介导的信号通路的影响

项目名称： 牛磺鹅去氧胆酸对大鼠肺泡巨噬细胞中TGR5受体介导的信号通路的影响

项目编号： No.31272605

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 李培锋

作者单位： 内蒙古农业大学

项目金额： 80万元

中文摘要： 申请者在前期研究中，揭示了体内活性物质牛磺鹅去氧胆酸（TCDCA）作为胆汁酸(BAs)的主要有效成分之一,对炎症与免疫功能均具有显著的调节作用。本课题旨在深入探讨TCDCA的抗炎与免疫调节作用的分子机制，探明TCDCA对胆汁酸受体TGR5介导的信号转导通路的影响。拟以NR8383大鼠肺泡巨噬细胞系为研究对象，采用荧光偏振、Western blot和荧光定量PCR等现代分子生物学技术揭示①TCDCA与TGR5的相互作用；②TCDCA对NR8383合成免疫相关因子过程中的细胞内信号转导通路的影响；③TCDCA对NR8383合成分泌免疫相关因子的影响；④TCDCA对TGR5介导的细胞膜电流及胞内[Ca2+]i的变化。通过该研究为研究抗炎免疫药物新的作用靶点提供实验依据。本研究对加快TCDCA转化成医药产品，提高动物胆汁的附加值和利用率，促进医药和畜牧业的发展均具有重要的现实意义。

中文关键词： 牛磺鹅去氧胆酸；胆汁酸受体；信号通路；环磷酸腺苷；蛋白激酶A

英文摘要： The early researches of applicant revealed that Taurochenodexyc acid (TCDCA), anactive substance, had effects of significant anti-inflammatory and immunoregulation. The aim of the research project is to investigate the molecular mechanisms of anti-inflammatory and immunoregulation effects of TCDCA and the influence of TCDCA on signaling pathway mediated by TGR5 in depth.The rat alveolar macrophage cell line NR8383 with the methods of modern molecular technology such as fluorescence polarization, western blot, real time PCR and etc. will be used to reveal: ①the interaction of TCDCA and TGR5; ②the influence of TCDCA on the signaling pathway during the relative immunologic factors synthesis process in the rat alveolar macrophage NR8383; ③the influence of TCDCA on synthesis and secretion of the relative immunologic factors in the rat alveolar macrophage NR8383; ④the influence of TCDCA and TGR5 agonist on the alteration of capacitance of cell membrane and [Ca2+]i. Through this study, it's able to provide an experimental basis for studying new target of immune-inflammatory drugs; and it has practical significance to accelerate TCDCA into pharmaceutical products, to improve the added value and utilization of animal bile, and to promote the development of medicine and animal husbandry.

英文关键词： TCDCA；TGR5；signal pathway；cAMP；PKA