| 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].Chinese Journal of Radiological Medicine and Protection,2025,45(11):1077-1084 |
| 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 |
| Received:August 07, 2025 |
| DOI：10.3760/cma.j.cn112271-20250807-00283 |
| KeyWords:FLASH irradiation Radiation-induced intestinal injury Intestinal crypt Dose-response effect |
| FundProject: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) |
| Author Name | Affiliation | E-mail | | Shen Yufeng | Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China | | | Zhou Jie | Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China
Department of Radiation Oncology, Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, University of Electronic Science and Technology of China, Chengdu 610041, China | | | Li Lintao | Department of Radiation Oncology, Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, University of Electronic Science and Technology of China, Chengdu 610041, China | | | Geng Fenghao | Department of Radiation Oncology, Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, University of Electronic Science and Technology of China, Chengdu 610041, China | | | Yang Chenxi | Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China | | | Chen Xiaohua | Department of Radiation Oncology, Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, University of Electronic Science and Technology of China, Chengdu 610041, China | | | Wang Shuo | Department of Radiation Oncology, Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, University of Electronic Science and Technology of China, Chengdu 610041, China | | | Tang Wei | School of Life Sciences and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China | | | Li Yongjie | School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China | | | Lu Shun | Department of Radiation Oncology, Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, University of Electronic Science and Technology of China, Chengdu 610041, China | lushun@scszlyy.org.cn |
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| Abstract:: |
| 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 (tcrypt=13.10, 23.80, 11.90; tmucosal=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. |
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