【摘要】 为了研究电离辐射对不同发育阶段人肺泡的损伤程度及机制，以人源肺泡类器官为模型，通过qRT-PCR、免疫荧光、Western blot、流式细胞术等生物学方法，比较辐射对不同发育阶段人肺类器官的形态、发育潜能、细胞死亡以及细胞类型的影响.结果表明：(1)定型内胚层阶段的细胞较干细胞更耐辐射，辐射引起其更少的细胞死亡；(2)芽尖祖类器官辐射后形态学发生明显变化，出现细胞向外迁移现象，同时随着辐射剂量增加，其逐渐丧失诱导形成肺泡类器官的能力；(3)肺泡类器官辐射后仍保持着原有形态学特征，但7天后，Ⅰ型肺泡细胞和Ⅱ型肺泡细胞的比例均显著下调，同时恶性转化相关基因也出现显著性变化，说明辐射对肺泡类器官的功能产生较长期的影响.总体而言，电离辐射对肺的发育有显著性影响，该研究为临床放射性肺损伤及修复提供了一定的理论依据.更多还原

【Abstract】 In order to study the damage and mechanism of ionizing radiation on human alveolar at different developmental stages, the authors used human alveolar organoids models, and biological methods such as qRT-PCR, immunofluorescence, Western blot and flow cytometry to compare the effects of radiation on the morphology, developmental potential, cell death and cell types of human lung-like organs at different developmental stages. The results showed that:(1) the definitive endoderm stage cells were more resistant to radiation and had less radiation-induced cell death than the stem cells;(2) radiation significantly altered the morphology of the lung progenitor organoids, with the appearance of outwardly migrating cells; and the lung progenitors organoids gradually lost their ability to form alveolar organoids with increasing radiation dose;(3) although the alveolar organoids retained normal morphological characteristics after radiation, the proportion of type Ⅰ and type Ⅱ epithelial cells was significantly down-regulated after 7 days, and malignant transformation-related genes were also significantly altered, indicating that radiation had long-term effects on the function of alveolar organoids. In conclusion, ionizing radiation has a significant effect on lung development, and this study provides a theoretical basis for clinical radiation lung injury and repair.更多还原