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一种具有肿瘤坏死因子抑制活性的合生菌可改善实验性空肠回肠黏膜损伤。

A Synbiotic with Tumor Necrosis Factor- Inhibitory Activity Ameliorates Experimental Jejunoileal Mucosal Injury.

机构信息

General Medicine and Community Health Science of the Sasayama Medical Center, Hyogo College of Medicine, Sasayama, Hyogo 669-2300, Japan.

Sagami Research Laboratory, Kanagawa 252-0231, Japan.

出版信息

Biomed Res Int. 2018 May 10;2018:9184093. doi: 10.1155/2018/9184093. eCollection 2018.

Abstract

Despite the recent development of biological modifiers for inflammatory bowel diseases (IBD), there continues to be considerable interest in fermented medicines because of its negligible adverse effects. We previously showed that the synbiotic Gut Working Tablet (GWT) alleviates experimental colitis. Here we show that GWT is capable of ameliorating jejunoileal mucosal injury, which is frequently seen with IBD. We created experimental jejunoileal mucositis in rats by injection of methotrexate (MTX) which increases intestinal permeability, a hallmark finding of IBD. Administering GWT to MTX-injected rats restored intestinal integrity by reversing villi shortening, crypt loss, and goblet cell depletion in the mucosa. Also GWT reduced activities of myeloperoxidase and lipid peroxidase and increased superoxide dismutase activity, which is critical for maintaining intestinal function. We further found that GWT suppressed mRNA expression of tumor necrosis factor- (TNF-) and interleukin-12 (IL-12) in macrophage and reduced TNF- mRNA expression in specimens with experimental colitis, which is in contrast to VSL#3 that enhanced TNF- production. Together, the current and previous animal studies clearly demonstrate the protective role of GWT in chemically induced enterocolitis. Crohn's disease, a well-known IBD, can affect any portion of the intestine, and these results suggest that GWT may be useful as a novel therapeutic or maintenance therapy for IBD.

摘要

尽管近年来生物调节剂在炎症性肠病(IBD)方面取得了进展,但由于其不良反应极小,因此人们对发酵药物仍有很大的兴趣。我们之前已经表明,共生 Gut Working Tablet(GWT)可缓解实验性结肠炎。在这里,我们展示了 GWT 能够改善常见于 IBD 的空肠回肠粘膜损伤。我们通过注射甲氨蝶呤(MTX)在大鼠中创建了实验性空肠回肠炎模型,该模型会增加肠通透性,这是 IBD 的一个标志发现。给予 GWT 可通过逆转绒毛缩短、隐窝丢失和粘膜中杯状细胞耗竭来恢复肠完整性。GWT 还降低了髓过氧化物酶和脂质过氧化物酶的活性,增加了超氧化物歧化酶的活性,这对于维持肠道功能至关重要。我们进一步发现,GWT 抑制了巨噬细胞中肿瘤坏死因子-(TNF-)和白细胞介素-12(IL-12)的 mRNA 表达,并降低了实验性结肠炎标本中 TNF-的 mRNA 表达,而 VSL#3 则增强了 TNF-的产生。总之,目前和以前的动物研究清楚地表明了 GWT 在化学诱导性肠炎中的保护作用。众所周知的 IBD 克罗恩病可以影响肠道的任何部位,这些结果表明 GWT 可能对 IBD 的治疗或维持治疗有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fae0/5971273/6dcdb85abed5/BMRI2018-9184093.001.jpg

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