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推进营养治疗:一种新型聚合物配方可减轻小鼠结肠炎模型中的肠道炎症,并抑制离体培养的炎症性结肠活检中的促炎细胞因子产生。

Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

机构信息

Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales Sydney, NSW, Australia.

Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales Sydney, NSW, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.

出版信息

Clin Nutr. 2017 Apr;36(2):497-505. doi: 10.1016/j.clnu.2016.01.010. Epub 2016 Jan 20.

DOI:10.1016/j.clnu.2016.01.010
PMID:26833290
Abstract

BACKGROUND & AIMS: Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF.

METHODS

Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF.

RESULTS

DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies.

CONCLUSIONS

Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients.

摘要

背景与目的

营养疗法是治疗克罗恩病(CD)的可行治疗选择。因此,改善营养疗法将使 CD 患者受益匪浅。本研究的目的是确定新型营养聚合物配方(PF)与现有标准 PF 的抗炎特性。

方法

利用葡聚糖硫酸钠(DSS)诱导 C57BL/6 小鼠结肠炎,将小鼠随机分为接受标准 PF 或新型 PF 加对照组。记录体重变化,并通过组织学和生化方法评估结肠损伤。还进行了其他实验,其中测量了儿科 CD 患者结肠活检暴露于标准 PF 或新型 PF 后的细胞因子反应。

结果

DSS 诱导了明显的体重减轻、结肠形态改变、髓过氧化物酶(MPO)活性增加以及肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-12 和单核细胞趋化蛋白(MCP)-1的结肠 mRNA 表达上调,以及相关的组织学变化。除了组织学损伤外,新型和标准 PF 均可逆转这些炎症变化。然而,新型 PF 但不是标准 PF 完全抑制了培养活检中的 TNF-α、IL-6 和 IL-8 水平。

结论

新开发的营养配方在小鼠模型中可重复性地改善 DSS 诱导的结肠炎,尽管与标准 PF 相比,这种反应没有明显差异。然而,新型 PF 在抑制培养结肠活检中炎症细胞因子释放方面明显更优。综上所述,这些发现支持新型 PF 在推进 CD 患者营养治疗中的可能作用。

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