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鼠坏死性小肠结肠炎模型中罗伊氏乳杆菌对肠道屏障功能的保护作用。

Protective Effects of Lactobacillus reuteri on Intestinal Barrier Function in a Mouse Model of Neonatal Necrotizing Enterocolitis.

机构信息

Department of Pediatrics, Yongchuan Hospital Affiliated to Chongqing Medical University, Chongqing, China.

Department of Pediatrics, Children's Hospital of Yongchuan District, Chongqing, China.

出版信息

Am J Perinatol. 2024 May;41(S 01):e386-e393. doi: 10.1055/s-0042-1755554. Epub 2022 Nov 11.

DOI:10.1055/s-0042-1755554
PMID:36368653
Abstract

OBJECTIVE

The intestinal mucosal and immune barriers play considerable roles in the pathogenesis of necrotizing enterocolitis (NEC). The present research was designed to assess the protective effects of (LR) DSM 17938 (LR 17938) on the intestinal barriers and its beneficial effects on inflammation in a neonatal mouse model of NEC.

STUDY DESIGN

Overall, 7-day-old 75 C57BL/6 neonatal mice were separated into three groups ( = 25) as follows: (1) control, (2) NEC, and (3) NEC + LR17938 (LR group). NEC mice were administered a hypertonic feeding formula and subjected to asphyxia and hypothermia. Hematoxylin and eosin (HE) staining and pathological scores were used to assess the pathological changes in the intestine. Oxidative stress was evaluated based on the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels were detected to assess inflammation. Gut permeability levels, bacterial translocation, and the levels of secretory idioglobulin A (sIgA), β-defensin, and tight junction (TJ) proteins were detected to evaluate gut mucosal and immune barrier function, and gut microbial diversity was detected to assess the composition of the gut flora.

RESULTS

LR 17938 administration decreased the NEC-induced increase in intestinal scores, mortality rate, gut damage, the MDA level, and TNF-α and IL-1β expressions. Besides, LR 17938 improved the survival rate of NEC mice. Moreover, LR 17938 administration improved gut permeability levels, SOD activity and the bacterial translocation, ameliorated the expression of TJ proteins, and improved the gut microbiota compared with those of NEC mice.

CONCLUSION

LR 17938 reduced intestinal inflammation and played a protective role in a neonatal animal model of NEC, possibly by regulating oxidative stress and exerting a protective effect on the gut mucosal and immune barriers.

KEY POINTS

· Our research indicated a protective effect of LR 17938 on gut barrier function in NEC mice.. · LR 17938may affect the diversity of gut flora, which are known to target beneficial bacteria.. · LR 17938 protected gut barrier function in the NEC pups by improving gut permeability..

摘要

目的

肠黏膜和免疫屏障在坏死性小肠结肠炎(NEC)的发病机制中起重要作用。本研究旨在评估 (LR)DSM 17938(LR 17938)对新生鼠 NEC 模型肠道屏障的保护作用及其对炎症的有益影响。

研究设计

总体而言,将 7 日龄 75 只 C57BL/6 新生小鼠分为三组(每组 25 只):(1)对照组,(2)NEC 组,(3)NEC+LR17938(LR 组)。NEC 组给予高渗喂养配方,并进行窒息和低体温处理。采用苏木精和伊红(HE)染色和病理评分评估肠道的病理变化。根据超氧化物歧化酶(SOD)和丙二醛(MDA)水平评估氧化应激。检测肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β水平评估炎症。检测肠道通透性、细菌易位和分泌型免疫球蛋白 A(sIgA)、β-防御素和紧密连接(TJ)蛋白水平评估肠道黏膜和免疫屏障功能,检测肠道微生物多样性评估肠道菌群组成。

结果

LR 17938 给药降低了 NEC 引起的肠道评分升高、死亡率、肠道损伤、MDA 水平以及 TNF-α和 IL-1β表达。此外,LR 17938 提高了 NEC 小鼠的存活率。此外,LR 17938 给药改善了肠道通透性、SOD 活性和细菌易位,改善了 TJ 蛋白的表达,并改善了 NEC 小鼠的肠道微生物群。

结论

LR 17938 减轻了新生动物模型 NEC 中的肠道炎症,并发挥了保护作用,可能是通过调节氧化应激对肠道黏膜和免疫屏障产生保护作用。

关键点

·我们的研究表明 LR 17938 对 NEC 小鼠的肠道屏障功能具有保护作用。·LR 17938 可能影响肠道菌群的多样性,已知肠道菌群靶向有益细菌。·LR 17938 通过改善肠道通透性来保护 NEC 幼鼠的肠道屏障功能。

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