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使用果寡糖进行预防和治疗性补充可改善氟尿嘧啶诱导的黏膜炎后的肠道稳态。

Prophylactic and therapeutic supplementation using fructo-oligosaccharide improves the intestinal homeostasis after mucositis induced by 5- fluorouracil.

机构信息

Departamento de Alimentos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

出版信息

Biomed Pharmacother. 2021 Jan;133:111012. doi: 10.1016/j.biopha.2020.111012. Epub 2020 Nov 27.

Abstract

The beneficial effects of prebiotic, such as fructo-oligosaccharides (FOS), in intestinal inflammation have been demonstrated in several studies. Herein, we evaluate whether joint treatment with FOS, both before and during mucositis, had additional beneficial effects and investigated the mechanisms underlying in the action of FOS on the intestinal barrier. BALB/c mice were randomly divided into five groups: CTR (without mucositis + saline solution), FOS (without mucositis + 6 % FOS), MUC (mucositis + saline solution), PT (mucositis + 6 % FOS supplementation before disease induction), and TT (mucositis + 6 % FOS supplementation before and during disease induction). Mucositis was induced by intraperitoneal injection (300 mg/kg) of 5-fluorouracil (5-FU). After 72 h, the animals were euthanized and intestinal permeability (IP), tight junction, bacterial translocation (BT), histology and morphometry, and immunoglobulin A secretory (sIgA), inflammatory infiltrate, and production of short-chain fatty acids (acetate, butyrate and propionate) were evaluated. The MUC group showed an increase in the IP, BT, and inflammatory infiltrate but a decrease in the tight junction expression and butyrate and propionate levels (P < 0.05). In the PT and TT groups, FOS supplementation maintained the IP, tight junction expression, and propionate concentration within physiologic levels, increased butyrate levels, and reduced BT and inflammatory infiltrate (P < 0.05). Total treatment with FOS (TT group) was more effective in maintaining histological score, morphometric parameters, and sIgA production. Thus, total treatment (prophylactic and therapeutic supplementation) with FOS was more effective than pretreatment alone, in reducing 5-FU-induced damage to the intestinal barrier.

摘要

在几项研究中,已经证明了益生元(如低聚果糖(FOS))对肠道炎症的有益作用。在此,我们评估了在黏膜炎发生之前和期间联合使用 FOS 是否具有额外的有益效果,并研究了 FOS 对肠道屏障作用的机制。BALB/c 小鼠随机分为五组:CTRL(无黏膜炎+生理盐水溶液)、FOS(无黏膜炎+6%FOS)、MUC(黏膜炎+生理盐水溶液)、PT(黏膜炎诱导前用 6%FOS 补充)和 TT(黏膜炎诱导前和期间用 6%FOS 补充)。通过腹腔内注射(300mg/kg)5-氟尿嘧啶(5-FU)诱导黏膜炎。72 小时后,处死动物并评估肠道通透性(IP)、紧密连接、细菌易位(BT)、组织学和形态计量学以及免疫球蛋白 A 分泌(sIgA)、炎症浸润和短链脂肪酸(乙酸盐、丁酸盐和丙酸盐)的产生。MUC 组表现出 IP、BT 和炎症浸润增加,但紧密连接表达和丁酸盐和丙酸盐水平降低(P<0.05)。在 PT 和 TT 组中,FOS 补充维持 IP、紧密连接表达和丙酸盐浓度在生理水平内,增加丁酸盐水平,并减少 BT 和炎症浸润(P<0.05)。FOS 的总治疗(TT 组)在维持组织学评分、形态计量参数和 sIgA 产生方面更有效。因此,与单独预处理相比,FOS 的总治疗(预防和治疗补充)在减少 5-FU 诱导的肠道屏障损伤方面更有效。

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