军事医学2025，Vol.49Issue(3)：171-177,7.DOI:10.7644/j.issn.1674-9960.2025.03.002
人肠器官芯片模型构建及其放射损伤效应评价研究
Evaluation of radiation-induced intestinal injury via a new human intestinal organ-on-a-chip model
摘要
Abstract
Objective To establish a human intestinal organ-on-a-chip model using a multi-array chip array to simulate the microphysiological structure of the human intestine and to investigate the impact of ionizing radiation on radiation-induced damage to human intestinal cells.Methods Caco-2 and human umbilical vein endothelial cells(HUVECs)were co-cultured in an organ chip.The cells were subjected to fluid shear stress via a precision shaker.After 7 days of dynamic culture,the morphological structure of intestinal epithelial cells and venous endothelial cells within the intestinal organ chip was examined using phase contrast microscopy,immunofluorescence staining,and confocal microscopy for three-dimensional(3D)imaging.γ-H2AX and TUNEL immunofluorescence staining were employed to assess DNA damage and apoptosis in intestinal epithelial cells two days post-irradiation.Villin immunofluorescence staining was used to evaluate villus height three days post-irradiation.EdU incorporation assay and Ki67 immunofluorescence staining were conducted to observe the effects of ionizing radiation on the proliferation of intestinal epithelial cells.Results After 7 days of dynamic culture,phase contrast microscopy and immunofluorescence staining combined with confocal 3D imaging revealed that the upper intestinal epithelial cells in the middle compartment of the chip formed a 3D intestinal villus structure,while the vascular endothelial cells in the lower compartment developed a vascular network structure.The chip was subsequently irradiated by 10 Gy X-ray.Immunofluorescence staining results indicated that the mean fluorescence intensity of γ-H2AX and TUNEL in the irradiated group was significantly higher than in the non-irradiated group 2 days after irradiation(P＜0.01),and that the proportion of EDU+and Ki67+cells in the irradiated group was significantly lower than in the non-irradiated group three days after irradiation(P＜0.05).Conclusion Caco-2 cells and HUVECs co-culture on an organ chip can generate the biomimetic structure of human intestinal villus.Ionizing radiation has been found to shorten intestinal villus,increase DNA damage and apoptosis in intestinal epithelial cells,and inhibit the proliferation of these cells.关键词
肠器官芯片/电离辐射/肠绒毛/DNA损伤/凋亡/增殖Key words
gut-on-a-chip/ionizing radiation/villus/DNA damage/apoptosis/proliferation分类
医药卫生引用本文复制引用
胡亮,吕琳,唐轩,王思涵,余祖胤,李艳华..人肠器官芯片模型构建及其放射损伤效应评价研究[J].军事医学,2025,49(3):171-177,7.基金项目
北京市自然科学基金项目(7242100) （7242100）
