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Antibiotic Alleviates Radiation-Induced Intestinal Injury by Remodeling Microbiota, Reducing Inflammation, and Inhibiting Fibrosis.
ACS Omega ( IF 4.1 ) Pub Date : 2020-02-05 , DOI: 10.1021/acsomega.9b03906
Zhenguo Zhao 1 , Wei Cheng 2 , Wei Qu 3 , Guoyi Shao 1 , Shuanghai Liu 1
Affiliation  

Radiation-induced intestinal injury is a common complication of abdominal radiation therapy. However, the pathological features of radiation-induced intestinal injury and its therapeutic regimen are not very clear. The aim of this study was to investigate the effects of antibiotic pretreatment on radiation-induced intestinal injury. Abdominal radiation disrupted the intestinal microbiota balance and significantly reduced bacterial diversity in mice. Antibiotic cocktail (Abx) pretreatment effectively removed the intestinal microbiota of mice, and metronidazole also reduced the diversity of intestinal bacteria to some extent. Two antibiotic pretreatment regimens improved the reconstitution ability of the gut microbiota in mice after radiation. Further experiments showed that Abx pretreatment effectively reduced the content of lipopolysaccharide (LPS) and inhibited the TLR4/MyD88/NF-κB signaling pathway in the ileum. In addition, Abx pretreatment regulated macrophage cell polarization in the ileum, downregulated TGF-β1, phosphorylated Smad-3 and α-SMA protein levels, and upregulated E-cadherin protein expression. Eventually, Abx pretreatment significantly improved the survival rate and attenuated intestinal injury of mice after radiation by reducing inflammation and preventing intestinal fibrosis. These results revealed that antibiotic pretreatment can effectively alleviate gut microbiota turbulence and intestinal damage caused by abdominal radiation in mice. Collectively, these findings add to our understanding of the pathogenesis of radiation enteritis.

中文翻译:

抗生素通过重塑微生物群,减少炎症和抑制纤维化来减轻辐射诱发的肠道损伤。

辐射诱发的肠损伤是腹部放射治疗的常见并发症。但是,放射线引起的肠损伤的病理特征及其治疗方案尚不清楚。这项研究的目的是研究抗生素预处理对辐射诱发的肠损伤的影响。腹部辐射破坏了肠道菌群的平衡,并显着降低了小鼠的细菌多样性。抗生素鸡尾酒(Abx)预处理可有效去除小鼠的肠道菌群,甲硝唑也可在一定程度上降低肠道细菌的多样性。两种抗生素预处理方案可改善放射后小鼠肠道菌群的重建能力。进一步的实验表明,Abx预处理可有效降低回肠中脂多糖(LPS)的含量并抑制TLR4 / MyD88 /NF-κB信号通路。此外,Abx预处理可调节回肠中的巨噬细胞极化,下调TGF-β1,磷酸化Smad-3和α-SMA蛋白水平,并上调E-钙粘蛋白蛋白表达。最终,Abx预处理通过减少炎症和预防肠道纤维化,显着提高了放疗后小鼠的存活率并减轻了肠道损伤。这些结果表明,抗生素预处理可以有效减轻小鼠腹部辐射引起的肠道菌群紊乱和肠道损伤。总的来说,这些发现增加了我们对放射性肠炎发病机理的认识。
更新日期:2020-02-18
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