Li Tuo,Ma Feifei,Guan Jiebing,et al.Indole-3-aldehyde-loaded inulin-based hydrogel for protection against radiation-induced intestinal injury[J].Chinese Journal of Radiological Medicine and Protection,2025,45(5):408-415
Indole-3-aldehyde-loaded inulin-based hydrogel for protection against radiation-induced intestinal injury
Received:November 05, 2024  
DOI:10.3760/cma.j.cn112271-20241105-00426
KeyWords:Radiation-induced intestinal injury  Inulin-based hydrogel  Indole-3-aldehyde  Intestinal microbiota
FundProject:国家自然科学基金(82001954,32071241,32171239);辐射防护实验室开放基金(CIRP-DTRI20220202)
Author NameAffiliationE-mail
Li Tuo School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261000, China
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China 
 
Ma Feifei School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261000, China
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China 
 
Guan Jiebing School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261000, China
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China 
 
Xie Siyu Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China  
Wang Ning School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261000, China
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China 
 
He Ningning School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261000, China
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China 
 
Song Huijuan School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261000, China
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China 
 
Li Jianguo School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261000, China  
Liu Qiang School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261000, China
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China 
liuqiang@irm-cams.ac.cn 
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Abstract::
      Objective To explore the protective effects and mechanisms of an indole-3-acetaldehyde (I3A)-loaded inulin-based hydrogel against radiation-induced intestinal injury. Methods The gelation properties and injectability of the I3A-loaded inulin-based hydrogel were detected using a rheometer, and its biocompatibility was assessed via a CCK-8 assay. Eighteen C57BL/6 mice (aged: 6-8 weeks) were stratified by body weight and randomly assigned into three groups with 6 mice in each group: blank control, irradiation-only, and irradiation+hydrogel protection. Abdominal irradiation was administered using 137Cs γ-rays at 17 Gy. The irradiation+hydrogel protection group received 200 μl/day of I3A-loaded inulin-based hydrogel for two days before and 2-3 days after irradiation. Meanwhile, the irradiation-only group was treated with an equivalent volume of sterile water via gavage. The mice were euthanized four days post-irradiation, and their intestinal tissues were harvested. Hematoxylin-eosin (HE) staining, Ki67 immunohistochemistry, and TUNEL immunofluorescence were performed to assess histopathological damage, epithelial cell proliferation, and apoptosis, respectively. Quantitative real-time PCR (qRT-PCR) was employed to measure mRNA levels of inflammatory and antioxidant factors. Gut microbiota composition was analyzed via 16S rRNA sequencing. Results The test results of the rheometer confirmed successful hydrogel formation. CCK-8 assays demonstrated excellent biocompatibility. Compared with the irradiation-only group, the irradiation+hydrogel protection group exhibited preserved intestinal histoarchitecture, a 1.5-fold increase in intestinal cell proliferation (t = 8.35, P < 0.05), and a 2-fold reduction in radiation-induced apoptosis (t = 7.94, P < 0.05). Moreover, the hydrogel group showed significantly elevated expression of the anti-inflammatory cytokine IL-10 and antioxidant factors NRF-2 and HO-1 (t = 3.16, 24.83, 5.92, P < 0.05), alongside reduced levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α (t = 5.15, 3.82, 3.83, P < 0.05). Gut microbiota analysis revealed significant modulation in microbial composition and abundance in the hydrogel group. Conclusions The I3A-loaded inulin-based hydrogel can significantly promote intestinal cell proliferation, reduce radiation-induced apoptosis, and enhance both anti-inflammatory and antioxidant responses. In addition, it regulates gut microbiota composition and abundance, protecting against radiation-induced intestinal injury.
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