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坏死性小肠结肠炎、短肠综合征和宫内生长受限猪模型中的肠道蛋白质组学

Intestinal proteomics in pig models of necrotising enterocolitis, short bowel syndrome and intrauterine growth restriction.

作者信息

Jiang Pingping, Sangild Per Torp

机构信息

Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark.

出版信息

Proteomics Clin Appl. 2014 Oct;8(9-10):700-14. doi: 10.1002/prca.201300097. Epub 2014 Jun 25.

Abstract

Necrotising enterocolitis (NEC), short bowel syndrome (SBS) and intrauterine growth restriction (IUGR) are three conditions associated with intestinal dysfunction in newborn infants, particularly those born preterm. Piglet (Sus scrofa) models have recently been developed for NEC, SBS and IUGR, and tissue proteomic analyses have identified unknown pathways and new prognostic disease markers. Intestinal HSPs, iron metabolism proteins and proteins related to amino acid (e.g. arginine) and glucose metabolism are consistently affected by NEC progression and some of these proteins are also affected by SBS and IUGR. Parallel changes in some plasma and urinary proteins (e.g. haptoglobin, globulins, complement proteins, fatty acid binding proteins) may mirror the intestinal responses and pave the way to biomarker discovery. Explorative non-targeted proteomics provides ideas about the cellular pathways involved in intestinal adaptation during the critical neonatal period. Proteomics, combined with other -omic techniques, helps to get a more holistic picture of intestinal adaptation during NEC, SBS and IUGR. Explorative -omic research methods also have limitations and cannot replace, but only supplement, classical hypothesis-driven research that investigate disease mechanisms using a single or few endpoints.

摘要

坏死性小肠结肠炎(NEC)、短肠综合征(SBS)和宫内生长受限(IUGR)是与新生儿肠道功能障碍相关的三种病症,尤其是早产新生儿。最近已针对NEC、SBS和IUGR开发了仔猪(Sus scrofa)模型,并且组织蛋白质组学分析已确定了未知途径和新的疾病预后标志物。肠道热休克蛋白、铁代谢蛋白以及与氨基酸(如精氨酸)和葡萄糖代谢相关的蛋白质持续受到NEC进展的影响,其中一些蛋白质也受到SBS和IUGR的影响。一些血浆和尿液蛋白质(如触珠蛋白、球蛋白、补体蛋白、脂肪酸结合蛋白)的平行变化可能反映肠道反应,并为生物标志物的发现铺平道路。探索性非靶向蛋白质组学为关键新生儿期肠道适应所涉及的细胞途径提供了思路。蛋白质组学与其他组学技术相结合,有助于更全面地了解NEC、SBS和IUGR期间的肠道适应情况。探索性组学研究方法也有局限性,不能替代但只能补充使用单一或少数终点来研究疾病机制的经典假设驱动研究。

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