Zhu Xiangzhan, Li Ya, Yue Lingling, Zhou Xinkui, Li Jianhui, Zhang Yaodong, Yu Zhidan, Liu Yuchun, Xu Ying, Wu Ling, Zhang Bianhong, Yang Minglei
Institute of Pediatric Medicine, Henan Children's Hospital, Zhengzhou Children's Hospital, Children's Hospital Affiliated of Zhengzhou University, Zhengzhou, Henan 450018, China.
Henan Key Laboratory of Rehabilitation Medicine, Henan Joint International Research Laboratory of Chronic Liver Injury, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Radiat Res. 2023 Mar 1;199(3):252-262. doi: 10.16667/RADE-22-00090.1.
Radiation-induced intestinal injury is one the most common adverse events of radiotherapy, which can severely affect quality of life. There are currently no effective preventive and therapeutic options for this disorder. Quercetin is a natural flavonoid found in common food species, with the characteristics of antioxidative, anti-inflammatory, and anti-cancerous activity. However, the role of quercetin on radiation-induced intestinal injury and the underlying mechanism remains poorly understood. In this study, we found quercetin treatment can improve the survival rate of mice after a single-dose (10 Gy) abdominal irradiation. Quercetin-pretreated mice significantly reduced radiation-induced DNA damage and intestinal epithelium cell apoptosis. In addition, quercetin also improved the proliferation activity of intestinal stem cells and promoted intestine epithelium repair after irradiation. Further studies demonstrated that quercetin treatment curtailed radiation-induced reactive oxygen species generation via regulating Nrf2 signaling in intestinal epithelium cells. Furthermore, treatment with Nrf2 inhibitor, could reverse the above effects. Altogether, quercetin can ameliorate radiation-induced intestine injury via regulating Nrf2 signaling, scavenging free radicals, and promoting intestinal epithelium repair.
放射性肠损伤是放射治疗最常见的不良事件之一,可严重影响生活质量。目前针对这种疾病尚无有效的预防和治疗方法。槲皮素是一种存在于常见食物中的天然类黄酮,具有抗氧化、抗炎和抗癌活性。然而,槲皮素对放射性肠损伤的作用及其潜在机制仍知之甚少。在本研究中,我们发现槲皮素处理可提高单次剂量(10 Gy)腹部照射后小鼠的存活率。经槲皮素预处理的小鼠可显著减少辐射诱导的DNA损伤和肠上皮细胞凋亡。此外,槲皮素还改善了肠道干细胞的增殖活性,并促进照射后肠上皮的修复。进一步研究表明,槲皮素处理通过调节肠上皮细胞中的Nrf2信号传导减少了辐射诱导的活性氧生成。此外,用Nrf2抑制剂处理可逆转上述效应。总之,槲皮素可通过调节Nrf2信号传导、清除自由基和促进肠上皮修复来改善放射性肠损伤。