| 杨雨晨,韩佳颖,李小波,等.重离子FLASH照射减轻急性肠道损伤及其调控机制[J].中华放射医学与防护杂志,2025,45(11):1092-1099.Yang Yuchen,Han Jiaying,Li Xiaobo,et al.Heavy-ion FLASH irradiation mitigates acute intestinal injury and its regulatory mechanisms[J].Chin J Radiol Med Prot,2025,45(11):1092-1099 |
| 重离子FLASH照射减轻急性肠道损伤及其调控机制 |
| Heavy-ion FLASH irradiation mitigates acute intestinal injury and its regulatory mechanisms |
| 投稿时间：2025-07-15 |
| DOI：10.3760/cma.j.cn112271-20250715-00252 |
| 中文关键词: 碳离子放射治疗 FLASH 放射性肠道损伤 双链断裂 转录组学 |
| 英文关键词:Carbon ion radiotherapy FLASH Radiation-induced intestinal injury Double-strand breaks Transcriptomics |
| 基金项目:国家重点研发计划(2022YFC2402304);国家自然科学基金(12305410);广州市科技局基础与应用基础研究专题(优秀博士"续航"项目,2025A04J2004) |
| 作者 | 单位 | E-mail | | 杨雨晨 | 中山大学肿瘤防治中心放疗科, 广州 510060
中山大学-国科离子放射治疗前沿技术联合实验室, 广州 510060 | | | 韩佳颖 | 中山大学肿瘤防治中心放疗科, 广州 510060
中山大学-国科离子放射治疗前沿技术联合实验室, 广州 510060 | | | 李小波 | 福建医科大学附属协和医院放射治疗科, 福州 350001 | | | 张俊昱 | 福建医科大学附属协和医院放射治疗科, 福州 350001 | | | 周利荣 | 兰州泰基离子技术有限公司, 兰州 730000 | | | 石健 | 中国科学院近代物理研究所, 兰州 730000 | | | 邓小武 | 中山大学肿瘤防治中心放疗科, 广州 510060
中山大学-国科离子放射治疗前沿技术联合实验室, 广州 510060 | | | 朱红玉 | 中山大学肿瘤防治中心放疗科, 广州 510060
中山大学-国科离子放射治疗前沿技术联合实验室, 广州 510060 | zhuhy@sysucc.org.cn |
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| 中文摘要: |
| 目的 研究碳离子FLASH照射(FLASH-RT)和常规剂量率照射(CONV-RT)后小鼠的急性肠损伤差异及调控机制。方法 将健康C57BL/6J小鼠27只按随机数表法抽取分为对照组(Control组)、FLASH-RT组(100 Gy/s)与CONV-RT组(0.1 Gy/s), 每组9只, 进行碳离子全腹照射。通过磷酸化组蛋白H2AX(γ-H2AX)、细胞核相关抗原67(Ki67)免疫组织化学检测DNA双链断裂(DSB)及细胞增殖;末端脱氧核苷酸转移酶介导dUTP缺口末端标记法(TUNEL)分析凋亡;结合转录组测序解析FLASH-RT和CONV-RT后分子通路差异。结果 与CONV-RT组相比, FLASH-RT组照射后3 h, 肠道γ-H2AX信号显著降低(t=3.80, P<0.01);照射后6 h肠道隐窝基底Ki67表达显著增加(t=4.30, P<0.001);照射后12 h TUNEL阳性细胞数减少(t=3.08, P<0.01)。转录组测序分析显示, FLASH-RT特异性激活胰岛素样生长因子(IGF)通路, 避免CONV-RT诱导的核因子κB(NF-κB)、B细胞受体炎症通路过度激活及能量代谢抑制。结论 相较于CONV-RT, 碳离子FLASH-RT可以减少DSB损伤, 保留肠道干细胞增殖活性, 且激活IGF通路及炎症、调控免疫及代谢通路, 从而显著减轻急性肠道上皮损伤。其中, DSB减少介导的修复通路调控与炎症通路抑制是潜在的正常组织保护机制。 |
| 英文摘要: |
| Objective To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT). Methods Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT. Results Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy (t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy (t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy (t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues. |
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