合成制剂对慢性肠病犬结肠超微结构和氧化应激的恢复作用。

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Dipak Kumar Sahoo, Tracey Stewart, Emily M Lindgreen, Bhakti Patel, Ashish Patel, Jigneshkumar N Trivedi, Valerie Parker, Adam J Rudinsky, Jenessa A Winston, Agnes Bourgois-Mochel, Jonathan P Mochel, Karin Allenspach, Romy M Heilmann, Albert E Jergens
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引用次数: 0

摘要

合成制剂可用于减轻慢性炎症性肠病(CIE)犬的肠道炎症和生态失调。先前的研究没有评估使用合生剂治疗的活跃CIE犬的结肠粘膜超微结构,也没有确定形态损伤与信号通路之间的可能关联。20只诊断为CIE的客户拥有的狗被随机分配接受水解饮食(安慰剂;PL)或添加合成igy (SYN)的水解日粮,持续6周。内镜下结肠活检进行组织病理学、超微结构和分子分析,并比较治疗前后。采用透射电镜(TEM)观察各组大鼠微绒毛长度(MVL)、线粒体(MITO)和粗内质网(ER)超微结构的变化。为了探索可能调节MITO和内质网应激的潜在信号通路,还进行了转录组学分析。治疗前后各犬粘膜超微结构病变程度不同。在治疗前,肠细胞、MVL、MITO和ER的形态学改变在PL和SYN狗之间没有显著差异。治疗后发现超微结构改变的显著变化,与pl治疗的狗相比,syn治疗的狗在MVL、MITO和ER损伤评分方面表现出显著改善。转录组学分析显示许多通路和关键基因与MITO和ER损伤相关。多种具有保护作用的信号通路及其相关基因,包括成纤维细胞生长因子2 (FGF2)、成纤维细胞生长因子7 (FGF7)、成纤维细胞生长因子10 (FGF10)、突触Ras GTPase激活蛋白1 (SynGAP1)、Ras鸟苷释放蛋白2 (RASGRP2)、Ras鸟苷释放蛋白3 (RASGRP3)、血小板反应蛋白1 (THBS1)、集落刺激因子1 (CSF1)、集落刺激因子3 (CSF3)、白细胞介素21受体(IL21R)、SYN治疗后,VI型胶原α 6链(COL6A6)、外胞浆异常蛋白A受体(EDAR)、叉头盒P3 (FoxP3)、卵泡抑制素(FST)、小颗粒蛋白1 (GREM1)、肌细胞增强因子2B (MEF2B)、神经调节蛋白1 (NRG1)、I型胶原α 1链(COL1A1)、肝细胞生长因子(HGF)、5-羟色胺受体7 (HTR7)、血小板衍生生长因子受体β (PDGFR-β)上调。差异基因表达与改善MITO和ER超微结构完整性和减少氧化应激有关。相反,其他具有有害作用的基因,如蛋白激酶camp活化的催化亚基β (PRKACB)、磷脂酶A2组XIIB (PLA2G12B)、钙调素1 (CALM1)、钙调素2 (CALM2)和白细胞介素18 (IL18),在SYN治疗后下调。在PL处理的狗中,PRKACB和CALM2等基因上调,而FGF2、FGF10、SynGAP1、RASGRP2、RASGRP3和IL21R等基因下调。CIE犬在诊断时有结肠超微结构病理,经合成治疗后有所改善。超微结构的改善与保护性基因的上调和有害基因的下调有关,这些基因通过多种信号通路介导其作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Restorative Effects of Synbiotics on Colonic Ultrastructure and Oxidative Stress in Dogs with Chronic Enteropathy.

Synbiotics can be used to reduce intestinal inflammation and mitigate dysbiosis in dogs with chronic inflammatory enteropathy (CIE). Prior research has not assessed the colonic mucosal ultrastructure of dogs with active CIE treated with synbiotics, nor has it determined a possible association between morphologic injury and signaling pathways. Twenty client-owned dogs diagnosed with CIE were randomized to receive either a hydrolyzed diet (placebo; PL) or a hydrolyzed diet supplemented with synbiotic-IgY (SYN) for 6 weeks. Endoscopic biopsies of the colon were obtained for histopathologic, ultrastructural, and molecular analyses and were compared before and after treatment. Using transmission electron microscopy (TEM), an analysis of the ultrastructural alterations in microvilli length (MVL), mitochondria (MITO), and rough endoplasmic reticulum (ER) was compared between treatment groups. To explore potential signaling pathways that might modulate MITO and ER stress, a transcriptomic analysis was also performed. The degree of mucosal ultrastructural pathology differed among individual dogs before and after treatment. Morphologic alterations in enterocytes, MVL, MITO, and ER were detected without significant differences between PL and SYN dogs prior to treatment. Notable changes in ultrastructural alterations were identified post-treatment, with SYN-treated dogs exhibiting significant improvement in MVL, MITO, and ER injury scores compared to PL-treated dogs. Transcriptomic profiling showed many pathways and key genes to be associated with MITO and ER injury. Multiple signaling pathways and their associated genes with protective effects, including fibroblast growth factor 2 (FGF2), fibroblast growth factor 7 (FGF7), fibroblast growth factor 10 (FGF10), synaptic Ras GTPase activating protein 1 (SynGAP1), RAS guanyl releasing protein 2 (RASGRP2), RAS guanyl releasing protein 3 (RASGRP3), thrombospondin 1 (THBS1), colony stimulating factor 1 (CSF1), colony stimulating factor 3 (CSF3), interleukin 21 receptor (IL21R), collagen type VI alpha 6 chain (COL6A6), ectodysplasin A receptor (EDAR), forkhead box P3 (FoxP3), follistatin (FST), gremlin 1 (GREM1), myocyte enhancer factor 2B (MEF2B), neuregulin 1 (NRG1), collagen type I alpha 1 chain (COL1A1), hepatocyte growth factor (HGF), 5-hydroxytryptamine receptor 7 (HTR7), and platelet derived growth factor receptor beta (PDGFR-β), were upregulated with SYN treatment. Differential gene expression was associated with improved MITO and ER ultrastructural integrity and a reduction in oxidative stress. Conversely, other genes, such as protein kinase cAMP-activated catalytic subunit beta (PRKACB), phospholipase A2 group XIIB (PLA2G12B), calmodulin 1 (CALM1), calmodulin 2 (CALM2), and interleukin-18 (IL18), which have harmful effects, were downregulated following SYN treatment. In dogs treated with PL, genes including PRKACB and CALM2 were upregulated, while other genes, such as FGF2, FGF10, SynGAP1, RASGRP2, RASGRP3, and IL21R, were downregulated. Dogs with CIE have colonic ultrastructural pathology at diagnosis, which improves following synbiotic treatment. Ultrastructural improvement is associated with an upregulation of protective genes and a downregulation of harmful genes that mediate their effects through multiple signaling pathways.

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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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