重金属人体生物有效性、吸收及毒性研究中的肠道细胞模型
Intestinal Cell Models for Heavy Metals Bioavailability, Absorption and Toxicity Investigation: A Review
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摘要: 重金属污染对人体健康产生极大威胁，因而备受关注。肠道吸收是人体重金属暴露的主要途径之一，因此，重金属的生物有效性、肠道吸收过程和毒性研究成为当前的研究热点。体外胃肠模拟法和动物模型被广泛用于重金属的相关研究，然而体外胃肠模拟法缺少人体肠道细胞成分，动物模型与人体存在着物种差异且实验成本高。鉴于此，研究者开发了能够部分模拟人体肠道上皮功能的体外肠道细胞模型。此模型作为研究生物有效性的重要工具，能模拟肠道对重金属的吸收转运过程，并能够结合分子生物学等技术、采用多学科交叉的研究方法探索重金属的肠吸收和肠毒性的分子机制。本文系统介绍了人肠上皮的结构功能、肠道上皮细胞对重金属吸收转运机制、肠道细胞模型的发展及其在重金属相关研究中的应用与优缺点，总结了肠细胞模型功能验证指标和优化方法。同时，还对肠道微流控培养系统（芯片肠道）和肠类器官等三维肠细胞模型技术的最新进展进行了介绍和展望。Abstract: Heavy metals poses great threats on human health, so people pay more attention to heavy metals pollution induced health risks in recent years. Intestinal absorption is one of the main routes for human exposure to heavy metals. Therefore, the investigations on bioavailability, intestinal absorption and toxicity of heavy metals attracted the scientific community. To systematically study the potential health risk of heavy metals, the in vitro gastrointestinal simulations and animal models have been widely used. However, due to the lack of human intestinal cells in gastrointestinal simulation methods and species differences between animal models and human, both of them have their limitations. Given that, the researchers developed an in vitro human intestinal cell model that partially mimics the in vivo human epithelium physiological functions. Based on the human intestinal cell models, the researchers could better investigate the bioavailability, intestinal absorption and transport of heavy metals. Besides, their related molecular mechanisms of intestinal absorption and toxicity can also be figured out via these new models combining with molecular biology techniques and interdisciplinary research methods. Collectively, this review systematically summarizes the structure and function of human intestinal epithelium, the intestinal absorption and transport mechanisms of heavy metals, the development process of intestinal cell models and their applications and limitations. In addition, the validation and optimization methods of intestinal cell models were analyzed. Furthermore, the state-of-the-art 3D intestinal cell models technology like the intestinal microfluidic culture system (Gut-on-a-chip) and intestinal organoids were also be introduced and prospected in this review.
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Key words:
- heavy metals /
- 3D intestinal cell model /
- bioavailability /
- co-culture model /
- toxicity
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