| 杨天宇,徐蒙蒙,胡文涛,张永胜,曹志飞.超高剂量率照射和常规照射对小鼠肝脏辐射损伤的转录组学比较研究[J].中华放射医学与防护杂志,2023,43(3):168-175 |
| 超高剂量率照射和常规照射对小鼠肝脏辐射损伤的转录组学比较研究 |
| Transcriptomic comparative study on mouse liver injury caused by ultra-high dose rate irradiation and conventional irradiation |
| 投稿时间：2022-11-30 |
| DOI：10.3760/cma.j.cn112271-20221130-00463 |
| 中文关键词: 超高剂量率照射 肝脏 RNA测序 基因表达 |
| 英文关键词:Ultra-high dose rate irradiation Liver RNA sequence Gene expression |
| 基金项目:省部共建放射医学与辐射防护国家重点实验室开放课题（GZK1202221）；苏州大学附属第二医院核技术医学应用重点人才项目（XKTJ-HRC2021002） |
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| 中文摘要: |
| 目的 研究超高剂量率照射（FLASH-RT）和常规照射（CONV-RT）对小鼠肝脏基因表达谱的影响，为揭示FLASH-RT的潜在作用机制提供理论依据。方法 将11只C57BL/6J雄性小鼠，按照随机数字法分为健康对照组（Ctrl组）、常规照射组（CONV-RT组）和超高剂量率照射组（FLASH-RT组）。CONV-RT组和FLASH-RT组采用相应的方式对小鼠进行腹部照射，剂量均为12 Gy，照后将小鼠脱颈处死，分别收集肝脏组织，提取总RNA。通过转录组测序技术和生物信息学分析方法，探究小鼠受照后肝脏组织基因表达谱变化。利用实时定量PCR法对3个基因（Stat1、Irf9和Rela）表达水平进行验证分析。结果 FLASH-RT组与CONV-RT组之间共发现1 762个差异表达基因（DEGs），其中上调基因660个，下调基因1 102个；FLASH-RT组与Ctrl组之间共发现1 918个差异表达基因，其中上调基因728个，下调基因1 190个；CONV-RT组与Ctrl组之间共发现1 569个差异表达基因，其中上调基因1 046个，下调基因523个。基因本体论（GO）分析显示，FLASH-RT组与CONV-RT组中的DEGs主要涉及对病毒的防御反应、细胞组分中的其他生物和分子功能中的腺苷转移酶活性等功能，FLASH-RT组与Ctrl组中的DEGs主要涉及对其他生物的防御反应、内质网伴侣复合物和双链RNA结合等功能。京都基因与基因组百科数据库（KEGG）分析显示，FLASH-RT组与CONV-RT组之间小鼠肝脏组织差异基因涉及甲型流感病毒及单纯疱疹病毒感染等多种通路，FLASH-RT组与Ctrl组之间小鼠肝脏组织差异基因涉及甲型流感病毒及NOD样受体信号通路等多种KEGG通路。实时定量PCR结果表明，FLASH-RT处理后，Stat1、Irf9和Rela mRNAs的表达水平显著升高（t=6.62、2.11、1.67，P<0.05）。结论 FLASH-RT和CONV-RT可引起小鼠肝脏组织中基因表达谱的改变，这些DEGs涉及多种放射生物学相关的功能通路，而FLASH-RT可以降低辐射引起的肝损伤，其机制可能与组织缺氧引起辐射抵抗有关。 |
| 英文摘要: |
| Objective To study the effects of FLASH irradiation (FLASH-RT) and conventional irradiation (CONV-RT) on gene expression profile in mouse liver, in order to provide theoretical basis of the potential mechanism of FLASH-RT.Methods A total of 11 C57BL/6J male mice were divided into healthy control group (Ctrl group), CONV-RT group and FLASH-RT group according to random number table method. Mouse abdomen was treated with 12 Gy CONV-RT or FLASH-RT. Then the mice were killed by neck removal, and the liver tissues were collected to extract total RNA for transcriptome sequencing (RNA-Seq) that was then analyzed by bio-informatics analysis to investigate the changes of gene expression profiles. The mRNA expression levels of Stat1, Irf9 and Rela were verified by quantitative real-time PCR assay.Results 1 762 differentially expressed genes (DEGs) were identified in group FLASH-RT vs. CONV-RT. Among them, 660 genes were up-regulated and 1 102 genes were down-regulated. 1 918 DEGs were identified in groups FLASH-RT vs. Ctrl. Among them, 728 genes were up-regulated and 1 190 genes were down-regulated. 1 569 DEGs were identified in group CONV-RT vs. Ctrl. Among them, 1 046 genes were up-regulated and 523 genes were down-regulated. According to Gene Ontology (GO) analysis, these DEGs from groups FLASH-RT vs. CONV-RT were involved in various functions including defense response to virus, other organisms in cell components, adenylyltransferase activity in molecular function activity. These DEGs from group FLASH-RT vs. Ctrl were involved in various functions including defense response to other oranisms, endoplasmic reticulum chaperone complex, double-stranded RNA binding and so on. These DEGs from group FLASH-RT vs. CONV-RT were involved in several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including influenza A, Herpes simplex infection and so on. These DEGs from group FLASH-RT vs. Ctrl were involved in several KEGG pathways including influenza A, NOD-like receptor signaling pathway. Stat1 was likely to be activated by FLASH radiation. The quantitative real-time PCR assay showed that FLASH-RT obviously increased the mRNA expressions of Stat1, Irf9 and Rela (t=6.62, 2.11, 1.67, P < 0.05).Conclusions FLASH-RT and CONV-RT could alter gene expression profiles in mouse liver tissues, and these DEGs are involved in multiple radiobiological functional pathways. In comparison with CONV-RT, FLASH-RT induces a low level of liver injury, which may due to hypoxia radiation resistance. |
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