| 刘小曼,刘雅妮,李志慧,等.FLASH照射对小鼠肠道急性放射损伤的机制研究[J].中华放射医学与防护杂志,2025,45(11):1085-1091.Liu Xiaoman,Liu Yani,Li Zhihui,et al.Mechanisms of FLASH irradiation on acute radiation-induced intestinal injury in mice[J].Chin J Radiol Med Prot,2025,45(11):1085-1091 |
| FLASH照射对小鼠肠道急性放射损伤的机制研究 |
| Mechanisms of FLASH irradiation on acute radiation-induced intestinal injury in mice |
| 投稿时间：2025-07-08 |
| DOI：10.3760/cma.j.cn112271-20250708-00238 |
| 中文关键词: 超高剂量率照射 X射线 FLASH效应 氧化应激 Nrf2-Keap1-HO-1通路 |
| 英文关键词:Ultra-high dose rate irradiation X-rays FLASH effect Oxidative stress Keap1-Nrf2-HO-1 signaling pathway |
| 基金项目: |
| 作者 | 单位 | E-mail | | 刘小曼 | 军事科学院军事医学研究院, 北京 100850
长江大学生命科学学院, 荆州 434025 | | | 刘雅妮 | 军事科学院军事医学研究院, 北京 100850 | | | 李志慧 | 军事科学院军事医学研究院, 北京 100850 | | | 闫栋斐 | 军事科学院军事医学研究院, 北京 100850 | | | 张利辉 | 军事科学院军事医学研究院, 北京 100850 | | | 李梦华 | 军事科学院军事医学研究院, 北京 100850 | | | 李少斌 | 长江大学生命科学学院, 荆州 434025 | | | 董国福 | 军事科学院军事医学研究院, 北京 100850 | | | 王长振 | 军事科学院军事医学研究院, 北京 100850 | wangcz2002@aliyun.com |
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| 中文摘要: |
| 目的 探讨超高剂量率(FLASH)与常规剂量率(CONV)脉冲X射线照射对小鼠小肠组织损伤模式的差异, 为超高剂量率脉冲X射线在胃肠放疗中的应用提供依据。方法 将32只C57BL/6J小鼠按随机数表法分为假照射组(SHAM)、常规剂量率组(CONV0.067和CONV0.1组)和超高剂量率组(F215组), 接受12 Gy单次腹部X射线照射, 剂量率分别为0、0.067、0.1、215 Gy/s, 每组8只。在辐射后第3天进行组织病理学(苏木精-伊红染色)、免疫组织化学和Western blot分析, 评估肠道组织的病理标志物、氧化应激指标及相关信号通路蛋白。结果 照射后第3天, 所有辐射组小鼠均出现不同程度的肠组织变性坏死、上皮脱落、绒毛缩短和隐窝消失(t=5.75、8.79、5.71, P< 0.05)。在氧化应激方面, 照后第3天, CONV0.067组和CONV0.1组的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-PX)、谷胱甘肽(GSH)和总抗氧化能力(T-AOC)水平较F215组显著降低(t=7.06~10.64, P< 0.01), 丙二醛(MDA)水平显著升高(t=11.06、8.31, P< 0.01), 而SHAM组与F215组差异无统计学意义(P>0.05)。免疫组织化学和Western blot结果显示, 第3天时, 与SHAM组相比, 各辐射组的Nrf2和HO-1蛋白水平呈上升趋势, Keap1蛋白水平呈下降趋势, 其中F215组与两常规剂量率组差异有统计学意义(t=4.89~20.95, P< 0.05), 这些结果均与前期抗氧化指标变化一致。结论 超高剂量率X射线照射通过减轻氧化应激与调控Keap1-Nrf2-HO-1通路表达, 降低肠道急性放射损伤。 |
| 英文摘要: |
| Objective To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy. Methods Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways. Results At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss (t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group (t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated (t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group (P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups (t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway. |
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