中华放射医学与防护杂志

申玉凤,周杰,李林涛,等.超高剂量率与常规剂量率全腹照射对小鼠急性放射性肠损伤的剂量效应差异[J].中华放射医学与防护杂志,2025,45(11):1077-1084.Shen Yufeng,Zhou Jie,Li Lintao,et al.Differences in dose-response effects between ultra-high dose rate and conventional dose rate whole abdominal irradiation on acute radiation-induced intestinal injury in mice[J].Chin J Radiol Med Prot,2025,45(11):1077-1084

超高剂量率与常规剂量率全腹照射对小鼠急性放射性肠损伤的剂量效应差异

Differences in dose-response effects between ultra-high dose rate and conventional dose rate whole abdominal irradiation on acute radiation-induced intestinal injury in mice

投稿时间：2025-08-07

DOI：10.3760/cma.j.cn112271-20250807-00283

中文关键词: FLASH照射放射性肠损伤肠隐窝剂量-效应

英文关键词:FLASH irradiation Radiation-induced intestinal injury Intestinal crypt Dose-response effect

基金项目:四川省科技项目(2024ZDZX0027);四川省自然科学基金(2025ZNSFSC0787);中央引导地方科技发展资金项目(2023ZYDF071)

作者	单位	E-mail
申玉凤	电子科技大学医学院四川省肿瘤医院·研究所, 成都 610054
周杰	电子科技大学医学院四川省肿瘤医院·研究所, 成都 610054 肿瘤精准放疗四川省重点实验室四川省肿瘤临床医学研究中心四川省癌症防治中心电子科技大学附属肿瘤医院放疗中心, 成都 610041
李林涛	肿瘤精准放疗四川省重点实验室四川省肿瘤临床医学研究中心四川省癌症防治中心电子科技大学附属肿瘤医院放疗中心, 成都 610041
耿凤豪	肿瘤精准放疗四川省重点实验室四川省肿瘤临床医学研究中心四川省癌症防治中心电子科技大学附属肿瘤医院放疗中心, 成都 610041
杨晨曦	电子科技大学医学院四川省肿瘤医院·研究所, 成都 610054
陈小花	肿瘤精准放疗四川省重点实验室四川省肿瘤临床医学研究中心四川省癌症防治中心电子科技大学附属肿瘤医院放疗中心, 成都 610041
王硕	肿瘤精准放疗四川省重点实验室四川省肿瘤临床医学研究中心四川省癌症防治中心电子科技大学附属肿瘤医院放疗中心, 成都 610041
唐炜	澳门科技大学医学院药学院, 澳门 999078
李永杰	电子科技大学生命科学与技术学院, 成都 610054
路顺	肿瘤精准放疗四川省重点实验室四川省肿瘤临床医学研究中心四川省癌症防治中心电子科技大学附属肿瘤医院放疗中心, 成都 610041	lushun@scszlyy.org.cn

摘要点击次数: 632

全文下载次数: 227

中文摘要:

目的探究超高剂量率(FLASH)较常规剂量率(CONV)X射线全腹照射(WAI)对小鼠急性放射性肠损伤的单次照射剂量-效应差异, 进一步探索最佳剂量参数及潜在机制。方法将186只雄性C57BL/6J小鼠按简单随机化法分为未照射组(6只)、FLASH组(90只)及CONV组(90只)。以11、12、13、14和15 Gy X射线单次WAI建立急性放射性肠损伤模型(FLASH 200 Gy/s, CONV 4 Gy/min)。评估照射后9 d内小鼠体质量及大便性状、疾病活动指数(DAI)的变化;11、12和13 Gy照射后第7天取肠道观察外观并测量长度, 选取小肠进行苏木精-伊红(HE)染色并定量分析各组小肠隐窝数目及黏膜上皮厚度。评估不同剂量WAI后15 d小鼠的生存情况。结果 11、12和13 Gy单次WAI后FLASH组小鼠体质量高于CONV组(t=10.17、12.65、10.16, P<0.05), FLASH组平均DAI分别为1.00±1.10、3.17±0.75和2.83±1.17, 低于CONV组的4.33±0.52、7.00±0和8.60±0.55(t=8.70、11.71、14.99, P<0.05)。而14和15 Gy WAI后FLASH组与CONV组体质量及DAI比较, 差异均无统计学意义(P＞0.05)。照射后第7天, 在11、12和13 Gy相同单次剂量下, FLASH照射组小鼠较CONV组肠道充血、水肿及短缩程度轻。11和13 Gy剂量下FLASH组小肠长度与CONV组(t=4.42、3.78, P＜0.05)及11和12 Gy剂量下FLASH组结直肠长度与CONV组(t=3.97、3.12, P＜0.05)差异具有统计学意义。小肠HE染色显示FLASH组较CONV组小肠绒毛长、隐窝数目多、黏膜上皮厚、结构更完整, 隐窝数目及黏膜上皮厚度差异均具有统计学意义(t_隐窝=13.10、23.80、11.90, t_黏膜=5.75、2.64、7.74, P<0.05)。照射后15 d, 15 Gy FLASH组小鼠生存率(50%)高于CONV组(10%)(χ² = 5.39, P<0.05), 中位生存期延长6 d(HR=0.340, 95%CI:0.115 4 ~ 0.999 9), 而11、12、13和14 Gy剂量FLASH组与CONV组比较差异均无统计学意义(P＞0.05)。结论 11、12和13 Gy FLASH组较CONV组减轻了中等单次剂量X射线WAI诱导的急性放射性肠道损伤, 并有提高15 Gy较高单次剂量WAI后小鼠生存率的潜力。该效应可能与肠隐窝保留相关, 且存在剂量依赖性。

英文摘要:

Objective To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms. Methods A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group (n=6), FLASH irradiation groups (n=90), and CONV irradiation groups (n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group (t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group (P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy (t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy (t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant (t_crypt=13.10, 23.80, 11.90; t_mucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ²=5.39, P<0.05), with a median survival extension of 6 d (HR=0.340, 95% CI: 0.1154-0.9999). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy (P>0.05). Conclusions FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.

HTML 查看全文查看/发表评论下载PDF阅读器

关闭