基于转录组学的归芪益元膏对~(12)C~(6+)束辐射损伤大鼠肺肾旁效应的作用机制
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摘要
目的:探讨归芪益元膏对~(12)C~(6+)束辐射损伤大鼠旁效应的防护机制。方法:采用~(12)C~(6+)束照射大鼠右侧肺部构建辐射损伤动物模型,分层随机分为单纯辐射组、归芪益元膏组,同时设立正常对照组,取大鼠的左肺、左肾组织以提取总RNA,IlluminaHiSeq平台测序,检测各组大鼠所有基因转录本的差异表达,筛选出与旁效应保护相关的基因及代谢途径。结果:给予归芪益元膏能改善~(12)C~(6+)束辐射损伤大鼠旁效应,转录数据分析显示其作用机制主要涉及肿瘤坏死因子、细胞外基质、细胞-细胞黏附连接、钙离子、白细胞介素-1、4、8等蛋白基因表达上调/下调。结论:归芪益元膏对~(12)C~(6+)束辐射损伤大鼠旁效应具有一定的防护作用,其机制可能与抑制电离辐射响应及癌症信号转导通路有关。
Objective: To investigate the protective mechanism of Guiqi Yiyuan Ointment on the bystander effect of ~(12)C~(6+)beam radiation injury in rats. Methods: ~(12)C~(6+) was used to irradiate the right lung of rats to construct an animal model of radiation injury. Rats were stratified and randomly divided into simple radiation group and Guiqi Yiyuan Ointment group. At the same time,Normal control group was also set up. Left lung and left kidney tissues of rats were taken to extract total RNA, and sequenced them on Illumina HiSeq platform. The differential expression of all transcripts in each group was detected. Screening for genes and metabolic pathways related to bystander effect protection. Results: Guiqi Yiyuan Ointment could improve the bystander effect of ~(12)C~(6+) beam radiation injury in rats. Transcriptional data analysis showed that the mechanism was mainly related to the up regulation/down regulation of protein and gene expressions, such as tumor necrosis factor, extracellular matrix, cell-cell adhesion junction, calcium ion, interleukin-1, 4, 8. Conclusion: Guiqi Yiyuan Ointment has a protective effect on the bystander effects of ~(12)C~(6+) beam radiation injury in rats. The mechanism may be related to the inhibition of ionizing radiation response and cancer signaling transduction pathway.
Objective: To investigate the protective mechanism of Guiqi Yiyuan Ointment on the bystander effect of ~(12)C~(6+)beam radiation injury in rats. Methods: ~(12)C~(6+) was used to irradiate the right lung of rats to construct an animal model of radiation injury. Rats were stratified and randomly divided into simple radiation group and Guiqi Yiyuan Ointment group. At the same time,Normal control group was also set up. Left lung and left kidney tissues of rats were taken to extract total RNA, and sequenced them on Illumina HiSeq platform. The differential expression of all transcripts in each group was detected. Screening for genes and metabolic pathways related to bystander effect protection. Results: Guiqi Yiyuan Ointment could improve the bystander effect of ~(12)C~(6+) beam radiation injury in rats. Transcriptional data analysis showed that the mechanism was mainly related to the up regulation/down regulation of protein and gene expressions, such as tumor necrosis factor, extracellular matrix, cell-cell adhesion junction, calcium ion, interleukin-1, 4, 8. Conclusion: Guiqi Yiyuan Ointment has a protective effect on the bystander effects of ~(12)C~(6+) beam radiation injury in rats. The mechanism may be related to the inhibition of ionizing radiation response and cancer signaling transduction pathway.
引文
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[15]李珍美玉,顾芸,易晟.细胞外基质在组织工程中的应用.交通医学,2014,28(5):425-429,432
[16]徐信.细胞连接.生物学通报,1986(7):22-24
[17]徐先祥,刁勇,许瑞安,等.植物多糖干预细胞黏附研究进展.药学学报,2012,47(7):844-849
[18]徐欢成,郑明学,古少鹏.钙信号转导对细胞凋亡的影响.动物医学进展,2013,34(1):112-115
[19]高昆,张连峰.白细胞介素与肿瘤研究进展.中国免疫学杂志,2012,28(5):467-469,473
[20]梁建庆,李金田,李娟,等.基于全基因组甲基化探讨辐射损伤大鼠的旁效应机制.中华中医药杂志,2018,33(11):5132-5136
[2]雷润宏,赵拓,吴国松,等.脑局部重离子辐射诱导大鼠外周旁效应研究.生命科学仪器,2015,13(12):24-30
[3]Kento N,Chika H,Tomomi W A,et al.In vivo 3D analysis of systemic effects after local heavy-ion beam irradiation in an animal model.Sci Rep,2016,6(10):1-9
[4]梁建庆,李金田,李娟,等.病证结合大鼠辐射损伤模型构建初探.中华中医药杂志,2017,32(5):2142-2145
[5]Langmead B,Trapnell C.Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.Genome Biology,2009,10(3):R25
[6]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人间的等效剂量换算.中国临床药理学与治疗学,2004,9(9):1069-1072
[7]Florea L,Song L,Salzberg S L.Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues.F1000 Research,2013,2:188
[8]刘奔波,龙颖,胡赛,等.辐射生物学旁效应研究热点及其进展.辐射研究与辐射工艺学报,2018,36(4):57-66
[9]梁建庆,李金田,李娟,等.归芪益元膏对重离子辐射损伤模型大鼠肺肾旁效应的影响.解放军医学杂志,2017,42(8):674-679
[10]梁建庆,李金田,李娟,等.归芪益元膏对12C6+束辐射损伤模型大鼠旁效应的影响.解放军医学杂志,2017,42(10):870-875
[11]雷润宏.重离子辐射神经损伤的旁效应研究.北京:北京理工大学,2015
[12]胡铮.辐射诱导mi R-320的表达调控及功能研究.北京:中国人民解放军军事医学科学院,2012
[13]何建成.中医学基础.北京:人民卫生出版社,2012:60
[14]赵玮,徐景杰.肿瘤坏死因子-α在炎症与肿瘤中的作用.中国疗养医学,2012,21(7):607-609
[15]李珍美玉,顾芸,易晟.细胞外基质在组织工程中的应用.交通医学,2014,28(5):425-429,432
[16]徐信.细胞连接.生物学通报,1986(7):22-24
[17]徐先祥,刁勇,许瑞安,等.植物多糖干预细胞黏附研究进展.药学学报,2012,47(7):844-849
[18]徐欢成,郑明学,古少鹏.钙信号转导对细胞凋亡的影响.动物医学进展,2013,34(1):112-115
[19]高昆,张连峰.白细胞介素与肿瘤研究进展.中国免疫学杂志,2012,28(5):467-469,473
[20]梁建庆,李金田,李娟,等.基于全基因组甲基化探讨辐射损伤大鼠的旁效应机制.中华中医药杂志,2018,33(11):5132-5136
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