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The effects of myeloablative or non-myeloablative total body irradiations on intestinal tract in mice.
Bioscience Reports ( IF 4 ) Pub Date : 2021-02-19 , DOI: 10.1042/bsr20202993
Shengyun Zhu 1, 2, 3 , Jing Liang 1 , Feng Zhu 1, 2, 3 , Xue Zhang 1 , Mengdi Xu 1 , Kai Zhao 1, 2, 3 , Lingyu Zeng 1, 2, 3 , Kailin Xu 1, 2, 3
Affiliation  

Acute radiation injury caused by high-dose radiation exposure severely impedes the application of radiotherapy in cancer management. To deeply understand the side effects of radiation on intestinal tract, an irradiation murine model was applied and evaluated. C57BL/6 mice were given 4Gy non-myeloablative irradiation, 8Gy myeloablative irradiation and non-irradiation (control), respectively. Results demonstrated that the 8Gy myeloablative irradiations significantly damaged the gut barrier along with decreasing MECA32 and ZO-1. However, a slight increase of MECA32 and ZO-1 was detected in the 4Gy non-myeloablative irradiations treatment from day 5 to day 10. Further, the irradiations affected the expression of P38 and JNK MAPK but not ERK1/2 MAPK signal pathway. Moreover, irradiation had adverse effects on hematopoietic system, altered the numbers and percentages of intestinal inflammatory cells. The IL-17/AhR had big increase in the gut of 4Gy irradiation mice at day 10 compared with other groups. Both 8Gy myeloablative and 4Gy non-myeloablative irradiation disturbed the levels of short chain fatty acids in intestine. Meanwhile, high dosage of irradiation decreased the intestinal bacterial diversity and altered the community composition. Importantly, the fatty acids generating bacteria Bacteroidaceae and Ruminococcaceae played key roles in community distribution and short chain fatty acids metabolism after irradiation. Collectively, the irradiation induced gut barrier damage with dosages dependent that led to the decreased p38 MAPK and increased JNK MAPK, unbalanced the mononuclear cells of gut, disturbed intestinal bacterial community and short chain fatty acids level.

中文翻译:

清髓性或非清髓性全身照射对小鼠肠道的影响。

高剂量辐射引起的急性辐射损伤严重阻碍了放射治疗在癌症治疗中的应用。为了深入了解辐射对肠道的副作用,应用并评估了辐射鼠模型。C57BL/6 小鼠分别接受 4Gy 非清髓性照射、8Gy 清髓性照射和非照射(对照)。结果表明,8Gy 清髓性照射显着损害肠道屏障,同时减少 MECA32 和 ZO-1。然而,从第 5 天到第 10 天,在 4Gy 非清髓性照射治疗中检测到 MECA32 和 ZO-1 略有增加。此外,照射影响 P38 和 JNK MAPK 的表达,但不影响 ERK1/2 MAPK 信号通路。此外,照射对造血系统有不良影响,改变了肠道炎症细胞的数量和百分比。与其他组相比,第 10 天 4Gy 照射小鼠肠道中的 IL-17/AhR 显着增加。8Gy 清髓性和 4Gy 非清髓性照射均扰乱了肠道中短链脂肪酸的水平。同时,高剂量照射降低了肠道细菌多样性并改变了群落组成。重要的是,产生脂肪酸的细菌拟杆菌科和瘤胃球菌科在辐照后的群落分布和短链脂肪酸代谢中起关键作用。总的来说,辐射诱导肠道屏障损伤,剂量依赖性导致 p38 MAPK 减少和 JNK MAPK 增加,肠道单核细胞失衡,扰乱肠道细菌群落和短链脂肪酸水平。
更新日期:2021-02-22
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