| Yang Tianyu,Xu Mengmeng,Hu Wentao,et al.Transcriptomic comparative study on mouse liver injury caused by ultra-high dose rate irradiation and conventional irradiation[J].Chinese Journal of Radiological Medicine and Protection,2023,43(3):168-175 |
| Transcriptomic comparative study on mouse liver injury caused by ultra-high dose rate irradiation and conventional irradiation |
| Received:November 30, 2022 |
| DOI：10.3760/cma.j.cn112271-20221130-00463 |
| KeyWords:Ultra-high dose rate irradiation Liver RNA sequence Gene expression |
| FundProject: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） |
| Author Name | Affiliation | E-mail | | Yang Tianyu | Department of Pathology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | Xu Mengmeng | Department of Pathology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | Hu Wentao | State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Suzhou Medical College of Soochow University, Suzhou 215123, China | | | Zhang Yongsheng | Department of Pathology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | Cao Zhifei | Department of Pathology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | hunancao@163.com |
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| Abstract:: |
| 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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