小肠类器官来源2D屏障模型作为药物吸收评价的新兴体外工具，具有人源性和组织来源特征，可在一定程度上弥补传统Caco-2细胞模型在细胞组成、转运体表达和代谢功能方面的局限。该模型可保留部分小肠上皮谱系特征及区域特异性表达模式，并在适当分化条件下呈现肽转运蛋白1（PEPT1）、P-糖蛋白（P-gp）等转运体表达和细胞色素P450 3A4酶（CYP3A4）等代谢酶活性，可用于药物渗透性评价、转运体功能验证、肠道首过代谢研究及毒性筛选。芯片平台可引入流体剪切力，多器官芯片可为研究吸收后代谢转化和器官间相互作用提供实验手段。该模型仍面临标准化不足、动物来源基质依赖、部分细胞类型难以长期维持、血管/免疫成分缺乏、微生物互作重建困难及多器官整合有限等挑战。未来，合成基质、多细胞共培养、微生物共培养、多器官芯片及人工智能辅助分析的发展，有望提升其在药物吸收、代谢、毒性评价和个体化用药研究中的应用价值。

Small intestinal organoid-derived 2D barrier models have emerged as promising in vitro tools for evaluating drug absorption. Owing to their human origin and tissue-specific characteristics, these models can partially overcome the limitations of conventional Caco-2 cell models in terms of cellular composition, transporter expression, and metabolic function. They retain some epithelial lineage features and region-specific expression patterns of the small intestine and, under appropriate differentiation conditions, exhibit the expression of transporters such as PEPT1 and P-gp, as well as metabolic enzyme activity such as CYP3A4. Therefore, they can be used for drug permeability assessment, transporter function validation, intestinal first-pass metabolism studies, and toxicity screening. Chip-based platforms can introduce fluid shear stress, while multi-organ chips provide experimental systems for investigating post-absorptive metabolic transformation and inter-organ interactions. Nevertheless, these models still face challenges, including insufficient standardization, dependence on animal-derived extracellular matrices, difficulty in maintaining certain cell types over the long term, lack of vascular and immune components, limited reconstruction of microbiota interactions, and insufficient multi-organ integration. In the future, the development of synthetic matrices, multicellular co-culture systems, microbiota co-culture technologies, multi-organ chips, and artificial intelligence-assisted analysis is expected to enhance their application value in drug absorption, metabolism, toxicity evaluation, and personalized medication research.

R965.1

天津市科技计划项目（24ZYCGSY00640） ；天津市科技计划项目（25YFKFYS00270）