摘要
目的 探索lncRNAs作为放射性肠损伤标志物的潜力。方法 15 Gy^(60)Co γ射线照射小鼠腹部,分析照射后72 h小鼠肠组织病理损伤情况以判断放射性肠损伤模型是否构建成功。利用实时荧光定量PCR验证小鼠空肠、空肠隐窝、结肠组织和血浆中候选辐射响应lncRNAs。0、5、10和15 Gy^(60)Co γ射线照射人小肠上皮细胞系HIEC-6和人结肠上皮细胞系NCM460,在照射后4、24、48和72 h检测候选lncRNAs表达水平随照射剂量的变化。结果 病理分析显示15 Gy局部照射成功建立急性放射性肠损伤小鼠模型,实时荧光定量PCR结果显示Dino、Lncpint、Meg3、Dnm^(3)os、Trp53cor1、Pvt1和Neat1能在放射性肠损伤发生后显著上调(P <0.05),其中小鼠血浆中Meg3和Dnm^(3)os在照射后显著上调(P <0.05),Gas5显著下调(P <0.05)。HIEC-6和NCM460细胞中DINO、MEG3、DNM3OS和GAS5表达水平在一定时间点存在剂量依赖性改变。结论 肠上皮细胞中的lncRNA MEG3、DNM3OS和GAS5更易响应电离辐射,且小鼠血浆及肠组织中能检测到一致的差异变化,有成为放射性肠损伤辐射生物标志物的潜力。
Objective:To explore the feasibility of long non-coding RNAs(lncRNAs)as biomarkers for radiation-induced intestinal injury.Methods:Mice were exposed to 15 Gy of ^(60)Coγ-rays to the abdominal area.The pathological changes in intestinal tissues were analyzed at 72 h post-irradiation to confirm the successful establishment of the radiation-induced intestinal injury model.Real-time quantitative PCR was conducted to detect the expression of candidate radiation-responsive lncRNAs in the jejunum,jejunal crypts,colon tissues,and plasma of irradiated mice.Human intestinal epithelial cell line HIEC-6 and human colon epithelial cell line NCM460 were exposed to 0,5,10,and 15 Gy of ^(60)Coγ-rays.The expression levels of candidate lncRNAs were measured at 4,24,48,and 72 h post-irradiation to observe their changes with the irradiation dose.Results:Pathological analysis showed that abdominal irradiation with 15 Gy successfully established an acute radiation-induced intestinal injury mouse model.Real-time quantitative PCR showed that Dino,Lncpint,Meg3,Dnm^(3)os,Trp53cor1,Pvt1,and Neat1 were significantly upregulated following the occurrence of radiation-induced intestinal injury(P<0.05).Among them,Meg3 and Dnm^(3)os in mouse plasma were significantly upregulated(P<0.05),while Gas5 was significantly downregulated(P<0.05).In HIEC-6 and NCM460 cells,the expression levels of DINO,MEG3,DNM3OS,and GAS5 showed dose-dependent patterns at certain time points(P<0.05).Conclusion:The lncRNAs encoded by MEG3,DNM3OS,and GAS5 in intestinal epithelial cells are responsive to ionizing radiation.Consistent differential expression changes were detected in mouse plasma and intestinal tissues,indicating their potential as biomarkers for radiation-induced intestinal injury.
作者
高莹
田雪蕾
刘青杰
赵骅
张伟
Ying GAO;Xuelei TIAN;Qingjie LIU;Hua ZHAO;Wei ZHANG(Key Laboratory of Radiological Protection and Nuclear Emergency,China CDC,National Institute for Radiological Protection,Chinese Center for Disease Control and Prevention,Beijing 100088 China)
出处
《中国辐射卫生》
2025年第2期270-278,共9页
Chinese Journal of Radiological Health
基金
中国疾病预防控制中心青年科学基金(2023A204)。
关键词
LncRNAs
放射性肠损伤
电离辐射
生物标志物
Long non-coding RNA
Radiation-induced intestinal injury
Ionizing radiation
Biomarker
作者简介
高莹(1998-),女,四川人,硕士研究生,研究方向放射性损伤、辐射生物效应。E-mail:1561611325@qq.com;通信作者:张伟,E-mail:zhangwei@nirp.chinacdc.cn。
