非离子型食品乳化剂增加邻苯二甲酸酯类吸收的效应及机制研究

The plasticizer DEHP is one of chemical contaminant in foods and recognized as endocrine disrupting chemicals (EDCs). There are numerous literatures of toxicokinetics on DEHP, but little research on ingredients food additives affecting the absorption, distribution and toxicity of DEHP. Great deals of food emulsifiers are utilized widely in the daily food. Based on some food emulsifiers can be used for improving the bioavailability of drugs in pharmaceuticals industry, we put forward the scientific hypothesis of the subject. Due to the effects on structure and function of intestinal mucosal cells, some food emulsifier may promote DEHP the absorption in the intestine and distribution in the toxicity target organ, thereby indirectly enhance the toxicity of DEHP. First, several commonly food emulsifiers are chosen to study the effects on the absorption and distribution for DEHP, in order to discriminate the type of food emulsifiers increased bioavailability of DEHP. Secondary, intensive and systematic research will be focused on the cellular and molecular mechanisms that these food emulsifiers increase bioavailability of DEHP. Then, in order to verify our hypothesis, we will carry out the long-term animal-feeding test of commercially daily food containing the food emulsifiers combined with DEHP exposure. Finally, we try to screen and evaluate some new indicators about the safety of food emulsifiers. The project will research the interaction of chemical contaminants in food and food ingredients and has significant academic value at elucidating the toxicity of DEHP from a novel perspective. The study achievements will be led into a new strategy for the intervention of DEHP on health damages. In addition, the project will afresh evaluate the potential health risks of food emulsifiers and have significant application value for the research and development of new food emulsifiers and for food safety risk assessment.

塑化剂DEHP是食品中化学污染物及内分泌干扰物。DEHP 的毒理学研究众多，但少有食品添加剂影响其吸收、分布与毒性的探讨。食品乳化剂（FE）广泛及大量地应用于日常食物。基于一些FE是制药工业提高药物生物利用度的辅料，提出本课题的假说。某些FE可能促进 DEHP的吸收及毒性靶器官的分布，从而对其毒性具有增效作用。首先探讨几种常用的FE是否影响DEHP吸收及靶器官分布、甄别增加DEHP吸收的FE类型；然后深入地探讨FE提高DEHP生物利用度的细胞分子机理；再以市售含有这些FE的食品进行联合DEHP染毒的长期动物喂养试验。最后筛选及初定评估FE安全性的一些新型指标。本项目将探讨食品添加剂与食品中化学污染物的交互影响，从一新颖角度阐述DEHP的毒理作用，具有重要学术价值；对DEHP损害健康的干预策略提出新的思路。重新审势FE潜在的健康风险，对研发新型FE及相关的食品安全风险评估具有实际应用价值。

以DEHP为代表的塑化剂是内分泌干扰物，也是常见的食品中化学污染物。食品乳化剂广泛及大量应用于日常饮食。本项目旨在探讨食品乳化剂促进 DEHP肠道吸收的效应及机理。主要研究内容及结果如下。.1. 合成了DEHP的主要代谢产物MEHP的荧光探针MEHP-AF。MEHP-AF可在动物整体、器官组织及细胞水平用于检测MEHP。具有快速方便、灵敏度高、原位示踪、以及无内源性干扰等优点。.2. 探讨了代表性的天然的及合成的非离子食品乳化剂，包括大豆磷脂、聚氧乙烯脱水山梨醇单油酸酯（P80）和单硬脂酸甘油酯（GMS），单次或长期暴露影响DEHP/MEHP吸收及靶器官分布的效应。 结果表明非离子型乳化剂具有更强的促进吸收作用，以P80的作用最强，可能与它具有更大的亲水-亲油平衡值（HBL）有关。.3. 探讨了非离子型乳化剂提高DEHP/MEHP生物利用度的细胞及分子机理。以肠道细胞（Caco-2 细胞与HT-29细胞）及在体肠道组织为研究对象，非离子型乳化剂能干扰肠道菌群的组成与丰度，降低肠粘膜屏障和粘液屏障相关蛋白（粘液蛋白粘蛋白-2、紧密连接蛋白claudin-1和occludin）的表达，改变了肠上皮细胞的完整性，增加肠粘膜的通透性。.4.以非离子型合成乳化剂喂养小鼠后收集肠道细菌，以此肠道细菌进行菌群移植试验。菌群定植完成后的小鼠经口暴露MEHP-AF。结果表明非离子型乳化剂相关的肠道细菌能明显促进MEHP-AF的吸收。.5. 进行了不同膳食模式联合DEHP/MEHP染毒的长期动物喂养试验，初步发现高脂饮食可促进DEHP/MEHP的吸收。. 这些发现对于评估某些食品乳化剂的安全风险，阐明化学污染物在食品中的吸收机理，指导食品乳化剂研发，以及公民对个人膳食管理具有重要意义。