中国医学科学院樊赛军等:3,3´-二吲哚甲烷缓解辐照引起的肠道损伤
创作:徐笑 审核:周旸 2018年11月11日
  • 3,3´-二吲哚甲烷(DIM)减轻全腹部辐照(WAI)引起的小鼠死亡或体重减轻状况,促进小肠修复,维持干细胞的增殖和分化;
  • DIM保护小肠绒毛细胞,增加小肠杯状细胞数量;
  • DIM缓解了WAI引起的Lgr5+小肠干细胞及其分化细胞的减少;
  • DIM提高抗氧化酶Nrf2的表达,清除活性氧,减少DNA损伤和细胞凋亡;
  • 体外细胞实验证明DIM提高人类肠细胞存活率,提高抗氧化酶活性;
  • DIM可恢复被WAI扰乱的小鼠肠道菌群结构。
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周旸
电离辐射导致的肠道损伤是癌症治疗以及核事故对可能人体造成的严重伤害,治疗手段有限。本研究利用小鼠模型和体外人肠道细胞,证明了3,3´-二吲哚甲烷可以缓解由辐射引起的肠道损伤,维护肠道结构和干细胞功能,恢复肠道菌群结构,具有临床参考价值。
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Amelioration of whole abdominal irradiation-induced intestinal injury in mice with 3,3´-Diindolylmethane (DIM)

3,3´-二吲哚甲烷缓解小鼠腹部由辐照引起的肠道损伤

10.1016/j.freeradbiomed.2018.10.410

2018-10-20, Article

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Ionizing radiation-induced intestinal injury is a catastrophic disease with limited effective therapies. 3,3´-Diindolylmethane (DIM), a potent antioxidant agent, has previously been shown to ameliorate hematopoietic injury in a murine model of total body radiation injury, but its effects on ionizing radiation-induced intestinal damage are not clear. Here, we demonstrate that administration of DIM not only protects mice against whole abdominal irradiation (WAI)-induced lethality and weight loss but also ameliorates crypt-villus structural and functional injury of the small intestine. In addition, treatment with DIM significant enhances WAI-induced reductions in Lgr5 ISCs and their progeny cells, including lysozyme Paneth cells, Villin enterocytes and Ki67 instantaneous amplifying cells, thus promoting small intestine repair following WAI exposure. Notably, the expression of Nrf2 increased, while the number of apoptotic cells and the expression of γH2AX decreased in the small intestines of DIM-treated mice compared to mice treated with vehicle following WAI. In vitro, we demonstrated that DIM protected human intestinal epithelial cell-6 (HIEC-6) against ionizing radiation, leading to increased cell vitality. Mechanistically, the radioprotective effect of DIM was likely attributable to its anti-DNA damage effects in irradiated HIEC-6 cells. Moreover, these changes were related to reduction in reactive oxygen species (ROS) levels and increased the activities of antioxidant enzymatic in irradiated HIEC-6 cells. Additionally, the DIM radioprotective effects on the intestine resulted in the restoration of the WAI-shifted gut bacteria composition in mice. Collectively, our findings demonstrate that the beneficial properties of DIM mitigate intestinal radiation injury, which provides a novel strategy for improving the therapeutic effects of irradiation-induced intestinal injury.

First Authors:
Lu Lu

Correspondence Authors:
Lu Lu,Saijun Fan

All Authors:
Lu Lu,Mian Jiang,Changchun Zhu,Junbo He,Saijun Fan

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