利用肠道类器官培养研究表皮调节素的抗辐射作用  

Establishment of an intestinal organoid-based method to investigate the radiation mitigation effect of Epiregulin

作　　者：富国祥 李远闯 潘梦雪 郭强 饶欣欣 徐小雅[1] 周轶[1] 邵春林[1] 高建军[1] 华国强[1] Fu Guoxiang;Li Yuanchuang;Pan Mengxue;Guo Qiang;Rao Xinxin;Xu Xiaoya;Zhou Yi;Shao Chunlin;Gao Jianjun;Hua Cuoqiang(Institute of Radiation Medicine,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学放射医学研究所,上海200032

出　　处：《中华放射医学与防护杂志》2018年第9期641-646,共6页Chinese Journal of Radiological Medicine and Protection

基　　金：国家自然科学基金（31470826,31670858）

摘　　要：目的利用小肠类器官3D培养技术研究表皮调节素（epiregulin）治疗辐射损伤的作用。方法采用乙二胺四乙酸二钠（EDTA）法分离小肠隐窝，以3D技术体外培养小肠类器官，培养24h后X射线照射．以碱性成纤维细胞生长因子（bFGF）作为阳性对照．研究建立小肠类器官辐射损伤模型。通过观察类器官存活率、大小和出芽等变化，研究表皮调节素对肠道类器官辐射损伤的治疗作用。结果体外培养的小肠类器官辐射后存活率与照射剂量相关，剂量曲线与体内辐射实验结果类似。照射后24h给药，表皮调节素可促进8Gyx射线照射后小肠类器官存活，400ng／ml组存活率为（12．56±1．02）％．较对照组（4．73±0．38）％明显增加，差异有统计学意义（t=12．43，P〈0．05）。结论表皮调节素在辐射后24h使用具有肠道类器官辐射损伤治疗作用。Objective To establish an intestinal organoid-based assay to investigate the radiation mitigation effect of epiregulin in vitro. Methods Intestinal crypts were released from tissue incubated with EDTA. Intestinal crypts seeded in 3D matrigel were irradiated at 24 h after plating. The radiation mitigation effect of epiregulin was evaluated by measuring the survival rate, size and budding numbers of the organoid after irradiation, and the basic FGF was used as a positive control of epiregulin. Results Radiation-induced lethality and dose-dependent survival curve of the intestinal organoid were consistent with in vivo data. Treatment with epiregulin （400 ng/ml） at 24 h post-radiation significantly increased survival rate of 8 Gy X-ray irradiated intestinal organoid in comparison with non-treated group [ （ 12. 56 ± 1.02）% vs. （4. 73 ±0. 38 ） %, t = 12. 43, P 〈 0. 05 ]. Conclusions Epiregulin has radiation mitigation effect on intestinal organoid and could serve as a potential medical countermeasure to mitigate gastrointestinal toxicity.

关 键 词：肠道干细胞 类器官 辐射 表皮调节素 肠型放射病 

分 类 号：R818.74[医药卫生—放射医学]