| Liu Xiaoman,Liu Yani,Li Zhihui,et al.Mechanisms of FLASH irradiation on acute radiation-induced intestinal injury in mice[J].Chinese Journal of Radiological Medicine and Protection,2025,45(11):1085-1091 |
| Mechanisms of FLASH irradiation on acute radiation-induced intestinal injury in mice |
| Received:July 08, 2025 |
| DOI：10.3760/cma.j.cn112271-20250708-00238 |
| KeyWords:Ultra-high dose rate irradiation X-rays FLASH effect Oxidative stress Keap1-Nrf2-HO-1 signaling pathway |
| FundProject: |
| Author Name | Affiliation | E-mail | | Liu Xiaoman | Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China
College of Life Sciences, Yangtze University, Jingzhou, Hubei 434025, China | | | Liu Yani | Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Li Zhihui | Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Yan Dongfei | Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Zhang Lihui | Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Li Menghua | Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Li Shaobin | College of Life Sciences, Yangtze University, Jingzhou, Hubei 434025, China | | | Dong Guofu | Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Wang Changzhen | Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | wangcz2002@aliyun.com |
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| Abstract:: |
| 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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