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载铜/锌蒙脱石影响断奶仔猪肠黏膜完整性及 LPS 攻毒后相关炎症基因、TLR4-MyD88 和 TGF-β1 信号通路的表达

Copper/zinc-loaded montmorillonite influences intestinal integrity, the expression of genes associated with inflammation, TLR4-MyD88 and TGF-β1 signaling pathways in weaned pigs after LPS challenge.

机构信息

Animal Science College, Zhejiang University, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou 310058, China.

出版信息

Innate Immun. 2017 Nov;23(8):648-655. doi: 10.1177/1753425917733033. Epub 2017 Sep 29.

Abstract

This study was aimed at investigating whether dietary copper/zinc-loaded montmorillonite (Cu/Zn-Mt) could alleviate Escherichia coli LPS-induced intestinal injury through pro- and anti-inflammatory signaling pathways (TLRs, NLRs and TGF-β1) in weaned piglets. Eighteen 21-d-old pigs were randomly divided into three groups (control, LPS and LPS + Cu/Zn-Mt). After 21 d of feeding, pigs in the LPS group and LPS + Cu/Zn-Mt group received i.p. administration of LPS, whereas pigs in the control group received saline. At 4 h post-injection, jejunum samples were collected for analysis. The results indicated that, compared with the LPS group, supplemental Cu/Zn-Mt increased transepithelial electrical resistance, the expressions of anti-inflammatory cytokines (TGF-β1) in mRNA and protein levels, and decreased FD4 and the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-8 and IL-1β). The pro-inflammatory signaling pathways results demonstrated that Cu/Zn-Mt supplementation decreased the mRNA levels of TLR4 and its downstream signals (MyD88, IRAK1, TRAF6) but had no effect on NOD1 and NOD2 signals. Cu/Zn-Mt supplementation did not affect NF-κB p65 mRNA abundance, but down-regulated its protein expression. The anti-inflammatory signaling pathways results showed supplemental Cu/Zn-Mt also increased TβRII, Smad4 and Smad7 mRNA expressions. These findings suggested dietary Cu/Zn-Mt attenuated LPS-induced intestinal injury by alleviating intestinal inflammation, influencing TLR4-MyD88 and TGF-β1 signaling pathways in weaned pig.

摘要

本研究旨在探讨饲粮铜锌负载蒙脱石(Cu/Zn-Mt)是否通过 Toll 样受体(TLRs)、Nod 样受体(NLRs)和转化生长因子-β1(TGF-β1)等促炎和抗炎信号通路缓解断奶仔猪大肠杆菌脂多糖(LPS)诱导的肠道损伤。将 18 头 21 日龄仔猪随机分为 3 组(对照组、LPS 组和 LPS+Cu/Zn-Mt 组)。饲养 21 d 后,LPS 组和 LPS+Cu/Zn-Mt 组仔猪腹腔注射 LPS,对照组仔猪注射生理盐水。注射后 4 h 采集空肠样品进行分析。结果表明,与 LPS 组相比,饲粮添加 Cu/Zn-Mt 提高了仔猪空肠上皮细胞紧密连接的完整性(以跨上皮电阻表示),降低了促炎细胞因子(FD4 和 TNF-α、IL-6、IL-8、IL-1β)mRNA 表达,增加了抗炎细胞因子(TGF-β1)mRNA 和蛋白表达。促炎信号通路结果表明,Cu/Zn-Mt 降低了 TLR4 及其下游信号分子(MyD88、IRAK1、TRAF6)的 mRNA 表达,但对 NOD1 和 NOD2 信号无影响。Cu/Zn-Mt 对 NF-κB p65 mRNA 丰度没有影响,但降低了其蛋白表达。抗炎信号通路结果表明,Cu/Zn-Mt 还增加了 TβRII、Smad4 和 Smad7 的 mRNA 表达。这些结果表明,饲粮添加 Cu/Zn-Mt 通过缓解肠道炎症、影响 TLR4-MyD88 和 TGF-β1 信号通路缓解 LPS 诱导的断奶仔猪肠道损伤。

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