Fe-Gly和Fe-CGly在小肠细胞中的吸收分子机制研究

Iron-deficiency anemia is a public health problem that frequently occurred in pregnant females and neonatal offspring. It is known as the major cause of hypoimmunity, disease susceptible and low growth rate, or even the sudden death of piglets. Maternal dietary supplementation of organic iron would significantly reduce the occurrence of iron-deficiency anaemia in piglets. Besides for the most widely used organic iron Fe-Gly, our earlier results also showed that the peptide chelate iron Fe-CGly, which designed from Fe-Gly could significantly improve the iron absorption and metabolism in piglets. However, the underlying mechanism of their transportation in intestinal is not clear. On this basis, this study intends to use the Fe-Gly and Fe-CGly as the subjects, to compare the transporting kinetic parameters and to find related carriers in pig IPEC-J2 and rat IEC-6 cells by sepecific inhibitors and RNA interfering in Transwell. All the works are to clarify how the two organic irons transported. The results of this study would help to reveal the particular way of organic iron absorption, to design new chelates and to control the iron-deficiency anaemia in farms.

缺铁性贫血症是一种常见的营养缺乏疾病，是新生仔猪免疫力低下、疾病易感、生长性能降低甚至猝死的重要原因之一。实践证明，在妊娠母猪日粮中添加螯合铁能显著提高铁的生物利用率，改善仔猪缺铁，但分子机理尚不明确。目前市场最常见的螯合铁是Fe-Gly，本课题组在Fe-Gly结构基础上开发了肽螯合铁Fe-CGly，两者均能显著改善机体铁吸收和代谢，有效预防动物缺铁。为揭示螯合铁的吸收机理，本项目以Fe-Gly和Fe-CGly为研究对象，采用IPEC-J2和IEC-6肠细胞Transwell转运模型，比较两者在肠细胞中的转运动力学参数，明确肠粘膜细胞的吸收机制；运用转运载体的抑制剂和RNAi方法，明确转运两者的关键转运载体及功能特性，阐明其在肠细胞中的吸收分子机制。本项目的开展不仅在阐明有机铁吸收转运机理方面具有重要的科学意义，也对有机铁产品开发和缺铁性贫血症的防治具有重要的实践价值。

缺铁性贫血症是一种常见的营养缺乏疾病，是新生仔猪免疫力低下、疾病易感、生长性能降低甚至猝死的重要原因之一。实践证明，在妊娠母猪日粮中添加螯合铁能显著提高铁的生物利用率，改善仔猪缺铁，但分子机理尚不明确。本项目选择甘氨酸铁（FeGly和FeBisGly）为研究对象，采用IPEC-J2细胞Transwell模型和类器官模型，揭示螯合铁的吸收机理。研究结果发现，FeBisGly增加杯状细胞MUC表达，且不与无机铁共用转运通道DMT1，通过同时增加铁的肠道驻留时间和转运效率，使得其具有比FeSO4和FeGly更高的转运效率。本项目的开展不仅在阐明有机铁吸收转运机理方面具有重要的科学意义，也对有机铁产品开发和缺铁性贫血症的防治具有重要的实践价值。