作为食品添加剂成分，纳米粒子对人类健康的长期影响需要更全面的评价。本项目拟探索食品中低剂量的二氧化钛纳米粒子（TiO2NP）的长期安全性和生物学效应，利用多种细胞和体内模型，揭示食物中的TiO2NP对脂代谢平衡和组织损伤修复的长期影响、作用途径和分子机制。申请人选取了两种粒径（50 nm和100 nm）的TiO2NP，发现50 nm粒径的TiO2NP分别在细胞水平和斑马鱼体内干扰TGFbeta信号通路的活性，促进脂肪细胞分化和脂肪形成，抑制肠上皮细胞的划痕愈合和斑马鱼尾部的损伤再生，而同样剂量的100 nm粒径的TiO2NP不产生明显的影响。本项目拟进一步研究通过食物进入小鼠体内的TiO2NP对脂代谢和肠损伤修复的影响，揭示其中的剂量-反应关系和干扰TGFbeta信号通路的分子机制，建立食品用纳米材料安全性的评估模型和评价体系，为食品中纳米成分的风险评估及相关标准制定提供科学理论依据。

As components of food additives, the long-term effects of nanoparticles on human health need comprehensive evaluation. This project aims to explore long-term safety and biological effects of low-dose titanium dioxide nanoparticles (TiO2NP) in diet, and discover how they affect lipid metabolism and tissue regeneration based on cell culture and in vivo models. We have found that 50 nm TiO2NP can interfere with TGFbeta signaling in cells and in Zebrafish, which in turn enhance adipocyte differentiation and adipogenesis, inhibit wound healing in intestinal epithelia cells and tail regeneration in Zebrafish, whereas 100 nm TiO2NP has no effect on these processes. We will further study these effects of TiO2NP in mice, explain their dosage-effect relationships and mechanisms to interfere with TGFbeta signaling, and provide evaluation models and systems for nano-safety in food industry.