Early weaning increases intestinal permeability, alters expression of cytokine and tight junction proteins, and activates mitogen-activated protein kinases in pigs
Early weaning increases intestinal permeability, alters expression of cytokine and tight junction proteins, and activates mitogen-activated protein kinases in pigs
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早期断奶会增加猪的肠道通透性，改变细胞因子和紧密连接蛋白的表达，并激活丝裂原激活蛋白激酶
DOI：
10.2527/jas.2012-5796
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发表时间：
2013-03-01
影响因子：
3.3
通讯作者：
Song, J.
中科院分区：
文献类型：
--
作者：
Hu, C. H.;Xiao, K.;Song, J.
尽管有报道称断奶应激会损害肠道屏障功能，但其机制尚未阐明。本研究评估了断奶后2周仔猪肠道的形态和通透性以及紧密连接蛋白和细胞因子的mRNA表达。测定 p38、c-Jun NH2 末端激酶 (JNK) 和细胞外调节激酶 (ERK1/2) 的磷酸化（激活）比率，以研究丝裂原激活蛋白激酶 (MAPK) 信号通路是否参与早期断奶过程。断奶后第 3 天和第 7 天观察到绒毛较短，隐窝较深。尽管受损的肠道形态在断奶后第 14 天恢复到断奶前的值，但肠粘膜屏障（通过上皮电阻 (TER) 和尤斯室中右旋糖酐 (4 kDa) 的细胞旁通量以及紧密连接蛋白表达反映）并未恢复。与断奶前阶段（第0天）相比，断奶后第3、7和14天空肠TER和occludin和claudin-1的mRNA表达量以及断奶后第3和7天的Zonula occlusionns-1（ZO-1）mRNA表达量减少，断奶后第3、7和14天右旋糖酐的细胞旁通量增加。与第 0 天相比，断奶后第 3 天和第 7 天肿瘤坏死因子-α (TNF-α) 和白细胞介素 - 6 (IL-6) mRNA 增加 (P < 0.05)，断奶后第 3 天干扰素-γ (IFN-γ) mRNA 增加 (P < 0.05)。与第 0 天相比，转化生长因子β 1 (TGF-β 1) 和观察断奶后白介素10（IL-10）mRNA的变化。断奶后第3天和第7天的JNK和p38磷酸化（激活）比例以及断奶后第3天的ERK1/2磷酸化比例较第0天升高（P < 0.05）。结果表明，早期断奶导致肠道屏障持续受损，紧密连接蛋白mRNA表达减少，促炎细胞因子表达上调，但抗炎细胞因子在断奶后肠道中不受影响。小猪。肠屏障功能的恢复慢于肠粘膜形态的恢复。断奶应激激活肠道MAPK信号通路，这可能是仔猪断奶相关肠道疾病的重要机制。 (C) 2013 年美国动物科学学会。版权所有。
Although weaning stress has been reported to impair intestinal barrier function, the mechanisms have not yet been elucidated. In the present study, the intestinal morphology and permeability and mRNA expressions of tight junction proteins and cytokines in the intestine of piglets during the 2 wk after weaning were assessed. The phosphorylated (activated) ratios of p38, c-Jun NH2-terminal kinase (JNK), and extracellular regulated kinases (ERK1/2) were determined to investigate whether mitogen-activated protein kinase (MAPK) signaling pathways are involved in the early weaning process. A shorter villus and deeper crypt were observed on d 3 and 7 postweaning. Although damaged intestinal morphology recovered to preweaning values on d 14 post-weaning, the intestinal mucosal barrier, which was reflected by transepithelial electrical resistance (TER) and paracellular flux of dextran (4 kDa) in the Ussing chamber and tight junction protein expression, was not recovered. Compared with the preweaning stage (d 0), jejunal TER and mRNA expressions of occludin and claudin-1 on d 3, 7, and 14 postweaning and Zonula occludens-1 (ZO-1) mRNA on d 3 and 7 postweaning were reduced, and paracellular flux of dextran on d 3, 7, and 14 postweaning was increased. An increase (P < 0.05) of tumor necrosis factor-alpha (TNF-alpha)and interleukin-6 (IL-6) mRNA on d 3 and d 7 postweaning and an increase (P < 0.05) of interferon-gamma (IFN-gamma) mRNA on d 3 postweaning were observed compared with d 0. No significant increase of transforming growth factor beta 1 (TGF-beta 1) and interleukin-10 (IL-10) mRNA after weaning was observed. The phosphorylated (activated) ratios of JNK and p38 on d 3 and 7 postweaning and the phosphorylated ratio of ERK1/2 on d 3 postweaning were increased (P < 0.05) compared with d 0. The results indicated that early weaning induced sustained impairment in the intestinal barrier, decreased mRNA expression of tight junction proteins, and upregulated the expression of proinflammatory cytokines, but antiinflammatory cytokines were not affected in the intestine of piglets. The recovery of the intestinal barrier function was slower than that of the intestinal mucosal morphology. The weaning stress activated MAPK signaling pathways in the intestine, which may be an important mechanism of weaning-associated enteric disorders of piglets. (C) 2013 American Society of Animal Science. All rights reserved.