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24 h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24 h给药,表皮调节素可促进8 Gy X射线照射后小肠类器官存活,400 ng/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24 h使用具有肠道类器官辐射损伤治疗作用.

abstractsObjective 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.