Heavy-ion FLASH irradiation mitigates acute intestinal injury and its regulatory mechanisms
10.3760/cma.j.cn112271-20250715-00252
- VernacularTitle:重离子FLASH照射减轻急性肠道损伤及其调控机制
- Author:
Yuchen YANG
1
;
Jiaying HAN
;
Xiaobo LI
;
Junyu ZHANG
;
Lirong ZHOU
;
Jian SHI
;
Xiaowu DENG
;
Hongyu ZHU
Author Information
1. 中山大学肿瘤防治中心放疗科，广州 510060
- Publication Type:Journal Article
- Keywords:
Carbon ion radiotherapy;
FLASH;
Radiation-induced intestinal injury;
Double-strand breaks;
Transcriptomics
- From:
Chinese Journal of Radiological Medicine and Protection
2025;45(11):1092-1099
- CountryChina
- Language:Chinese
-
Abstract:
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.
