miR-122-5p在γ射线照射致外周血白细胞损伤中的作用  

Effect of miR-122-5p on peripheral blood leukocytes injury induced byγirradiation

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作  者:吴慧翔 胡伟翔 关华 聂继盛[1] WU Hui-xiang;HU Wei-xiang;GUAN Hua;NIE Ji-sheng(School of Public Health,Shanxi Medical University,Taiyuan 030001,China;Institute of Radiation Medicine,Academy of Military Medical Sciences,Academy of Military Sciences)

机构地区:[1]山西医科大学公共卫生学院,太原030001 [2]军事科学院军事医学研究院辐射医学研究所

出  处:《环境卫生学杂志》2023年第6期416-423,共8页JOURNAL OF ENVIRONMENTAL HYGIENE

基  金:军队后勤科研重点项目(BWS18J008);国家自然科学基金资助项目(31800704)。

摘  要:目的研究不同剂量^(60)Coγ射线照射后,小鼠全血中miRNA分子标志物水平变化并进行验证,为确立miR-122-5p作为辐射损伤生物标志物提供实验依据。方法采用^(60)Coγ射线对BALB/c小鼠全身及人外周血进行不同剂量(0、1、2、4和6 Gy)的照射。对照射4 h后小鼠眼球血分离所得白细胞进行高通量测序,通过生物信息学筛选辐射敏感的miRNA,并对其靶基因进行预测和功能通路分析。进一步采用实时定量PCR(qPCR)技术检测小鼠全血白细胞和人外周血淋巴细胞中辐射敏感miRNA的表达变化。结果对测序结果进行分析,共筛选出5个具有统计学意义(p<0.05)辐射敏感miRNA,分别为miR-150-5p、miR-150-3p、miR-6916-5p、miR-122-5p和miR-212-3p。生物信息学结果表明,辐射敏感miRNA的靶基因主要涉及AMPK信号通路,凋亡,自噬和PI3K-Akt信号通路等。RT-PCR结果显示,miR-150-5p和miR-122-5p的表达在小鼠全血白细胞和人外周血淋巴细胞中具有明显的剂量—效应关系。结论miR-122-5p是潜在的辐射损伤生物标志物。Objective To investigate and validate the changes of miRNA molecular markers in whole blood of mice after exposure to different doses of ^(60)Coγ-rays,and to provide an experimental basis for establishing miR-122-5p as a biomarker of radiation damage.Methods The whole body of BALB/c mice and human peripheral blood were irradiated with ^(60)Coγ-rays at different doses(0,1,2,4,and 6 Gy).Leukocytes were isolated from the eyeball blood of mice after 4 h irradiation for high-throughput sequencing,and then the radiation-sensitive miRNAs were screened by bioinformatics,followed by target gene prediction and functional pathway analysis.Quantitative PCR(qPCR)was used to detect the expression changes of radiation-sensitive miRNAs in the whole blood leukocytes of mouse and peripheral-blood lymphocytes of human.Results The sequencing result showed a total of five radiation-sensitive miRNAs were obtained with statistical significance(P<0.05),which were miR-150-5p,miR-150-3p,miR-6916-5p,miR-122-5p,and miR-212-3p,respectively.Bioinformatics result indicated that the target genes of the radiation-sensitive miRNAs were mainly involved in the AMPK signaling pathway,apoptosis,autophagy,and the PI3K-Akt signaling pathway.qPCR result showed that the expression of miR-150-5p and miR-122-5p had significant dose-response effects in the whole blood leukocytes of mouse and peripheral-blood lymphocytes of human.Conclusion miR-122-5p is a potential biomarker of radiation-induced damage.

关 键 词:电离辐射 生物标志物 高通量测序 实时定量PCR(qPCR) 剂量效应 

分 类 号:R14[医药卫生—公共卫生与预防医学]

 

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