Ghrelin/GHS-R系统调控羊IGF-I分泌机制的研究

Ghrelin主要分泌于胃，可促进生长激素（GH）分泌；胰岛素样生长因子-I（IGF-I）主要产生于肝脏，可介导GH调控机体生长发育。本团队之前研究表明外源性Ghrelin可升高羊血液GH和IGF-I水平，然而Ghrelin调控IGF-I途径及其机制尚不清楚。本项目以绵羊为研究对象，通过在体肝脏靶向输注外源性Ghrelin、Ghrelin抗体或皱胃汇入肝脏血管支暂时性结扎而阻断内源性Ghrelin等策略，揭示Ghrelin对肝脏IGF-I水平的影响；在羊原代肝细胞揭示Ghrelin是否直接促进肝细胞IGF-I的分泌及可能的细胞信号途径；定位与定量Ghrelin、IGF-I及它们特异性受体蛋白或基因在各组织的分布与表达，尤其是IGF-I表达量高的细胞上是否有Ghrelin特异性受体的定位，为判定Ghrelin是否直接调控IGF-I的分泌提供组织学依据，最终为完善反刍动物生长调控理论提供参考。

Ghrelin is mainly secreted from the stomach and can promote the secretion of growth hormone (GH); insulin-like growth factor-I (IGF-I) is mainly produced in the liver and can mediate the function of GH in regulating animal growth. Our previous study showed that exogenous ghrelin increased the plasma GH and IGF-I levels in sheep. However, the pathway and mechanism of ghrelin regulating IGF-I levels are still unclear. This project aims to targetly infuse of exogenous ghrelin to the liver or temporary ligation of the gastric vasculature into the liver to block endogenous ghrelin to reveal the effect of ghrelin on liver IGF-I levels in sheep; in ovine primary hepatocytes, it will be revealed whether ghrelin directly promotes the secretion of hepatocyte IGF-I and its possible cell signaling pathway; localization and quantification of ghrelin, IGF-I and their specific receptor proteins or genes in sheep tissues, especially whether there is ghrelin specific receptor GHS-R1a on the cells with high expression of GF-I will be studied. Those results will provide histological basis for determining whether ghrelin directly regulates the secretion of IGF-I, and finally improves the growth regulation theory in ruminants.