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中链甘油三酯通过抑制脂多糖刺激的断奶仔猪的 toll 样受体 4、核苷酸结合寡聚化结构域蛋白和坏死性凋亡信号通路来改善肠道完整性。

Medium-chain TAG improve intestinal integrity by suppressing toll-like receptor 4, nucleotide-binding oligomerisation domain proteins and necroptosis signalling in weanling piglets challenged with lipopolysaccharide.

机构信息

Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.

出版信息

Br J Nutr. 2018 May;119(9):1019-1028. doi: 10.1017/S000711451800003X. Epub 2018 Mar 6.

Abstract

This study was conducted to evaluate whether medium-chain TAG (MCT) could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by regulating intestinal epithelial inflammatory response, as well as necroptosis. A total of twenty-four weanling piglets were randomly allotted to one of four treatments in a 2×2 factorial arrangement including diet type (5 % maize oil v. 4 % MCT+1 % maize oil) and immune stress (saline v. E. coli LPS). The piglets were fed diets containing maize oil or MCT for 21 d. On 21 d, piglets were injected intraperitoneally with saline or LPS. The blood and intestinal samples were collected at 4 h post injection. Supplementation with MCT improved intestinal morphology, digestive and barrier function, indicated by increased jejunal villus height, increased jejunal and ileal disaccharidases (sucrase and maltase) activities, as well as enhanced protein expression of claudin-1. Furthermore, the protein expression of heat-shock protein 70 in jejunum and the concentration of TNF-α in plasma were reduced in the piglets fed diets supplemented with MCT. In addition, MCT down-regulated the mRNA expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerisation domain proteins (NOD) signalling-related genes in jejunum and ileum. Finally, MCT inhibited jejunal and ileal enterocyte necroptosis indicated by suppressed mRNA expression of the receptor-interacting protein 3 and mixed-lineage kinase domain-like protein. These results indicate that MCT supplementation may be closely related to inhibition of TLR4, NOD and necroptosis signalling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.

摘要

本研究旨在评估中链甘油三酯(MCT)是否通过调节肠道上皮炎症反应以及坏死性凋亡来缓解大肠杆菌脂多糖(LPS)诱导的肠道损伤。将 24 头断奶仔猪随机分为 4 种处理组中的一种,采用 2×2 析因设计,包括日粮类型(5%玉米油与 4% MCT+1%玉米油)和免疫应激(生理盐水与 LPS)。仔猪饲喂含有玉米油或 MCT 的日粮 21 d。第 21 天,仔猪腹膜内注射生理盐水或 LPS。注射后 4 h 采集血液和肠道样品。补充 MCT 可改善肠道形态、消化和屏障功能,表现为空肠绒毛高度增加,空肠和回肠二糖酶(蔗糖酶和麦芽糖酶)活性增加,以及紧密连接蛋白-1 的蛋白表达增强。此外,MCT 可降低饲粮补充 MCT 仔猪空肠热休克蛋白 70 的蛋白表达和血浆 TNF-α 的浓度。此外,MCT 下调了空肠和回肠 TLR4 和核苷酸结合寡聚化结构域蛋白(NOD)信号相关基因的 mRNA 表达。最后,MCT 抑制了空肠和回肠肠上皮细胞坏死性凋亡,表现为受体相互作用蛋白 3 和混合谱系激酶结构域样蛋白的 mRNA 表达受到抑制。这些结果表明,MCT 补充可能与 TLR4、NOD 和坏死性凋亡信号通路的抑制以及在炎症状态下肠道完整性的改善密切相关。

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