Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-β1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge
Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-β1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge
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乳清蛋白浓缩物增强肠道完整性，并影响脂多糖挑战后仔猪的转化生长因子-β1 和丝裂原激活蛋白激酶信号通路
DOI：
10.1017/s0007114515005085
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发表时间：
2016-03-28
影响因子：
3.6
通讯作者：
Han, Xinyan
中科院分区：
文献类型：
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作者：
Xiao, Kan;Jiao, Lefei;Han, Xinyan
乳清蛋白浓缩物（WPC）已被报道对肠道屏障具有保护作用。然而，所涉及的分子机制尚未完全阐明。转化生长因子-β 1（TGF-β 1）是WPC中的重要成分，但TGF-β 1是否在这些过程中发挥作用尚不清楚。本研究的目的是研究WPC对肠上皮屏障的保护作用，以及TGF-β 1是否参与了脂多糖（LPS）攻击后的仔猪模型中的这些保护过程。总共将18头断奶仔猪随机分配至以下三个处理组之一：（1）未攻击对照和对照饮食;（2）LPS攻击对照和对照饮食;（3）LPS +5%WPC饮食。饲喂对照组和5%WPC组19 d后，分别注射LPS和生理盐水.在注射后4 h，处死猪以收获空肠样品。结果表明，与LPS组相比，WPC组小肠绒毛高度和绒毛高度与隐窝深度比值均显著增加（P < 0.05），肠屏障功能显著改善（P < 0.05），表现为跨上皮电阻增加和葡聚糖（4kDa）的粘膜-浆膜-细胞间流量减少。WPC还能抑制LPS诱导的空肠粘膜claudin-1、occludin和zonula occludens-1表达的降低（P < 0.05）。WPC还减轻了肠道炎症，表现为TNF-α、IL-6、IL-8和IL-1 β的mRNA表达降低（P < 0.05）。补充WPC也增加了TGF-β 1蛋白、磷酸化Smad 2表达及Smad 4、Smad 7 mRNA表达均降低（P < 0.05）（P< 0.05）磷酸化的c-jun N-末端激酶（JNK）和p38（磷酸化JNK：JNK和p-p38：p38），而增加（P < 0.05）细胞外信号调节激酶（ERK）的比例（磷酸化ERK：ERK）。总的来说，这些结果表明，膳食中包含WPC通过改善粘膜屏障功能、减轻肠道炎症和影响TGF-β 1经典Smad和丝裂原活化蛋白激酶信号通路来减轻LPS诱导的肠道损伤。
Whey protein concentrate (WPC) has been reported to have protective effects on the intestinal barrier. However, the molecular mechanisms involved are not fully elucidated. Transforming growth factor-beta 1 (TGF-beta 1) is an important component in the WPC, but whether TGF-beta 1 plays a role in these processes is not clear. The aim of this study was to investigate the protective effects of WPC on the intestinal epithelial barrier as well as whether TGF-beta 1 is involved in these protection processes in a piglet model after lipopolysaccharide (LPS) challenge. In total, eighteen weanling pigs were randomly allocated to one of the following three treatment groups: (1) non-challenged control and control diet; (2) LPS-challenged control and control diet; (3) LPS + 5 % WPC diet. After 19 d of feeding with control or 5 % WPC diets, pigs were injected with LPS or saline. At 4 h after injection, pigs were killed to harvest jejunal samples. The results showed that WPC improved (P < 0.05) intestinal morphology, as indicated by greater villus height and villus height: crypt depth ratio, and intestinal barrier function, which was reflected by increased transepithelial electrical resistance and decreased mucosal-to-serosal paracellular flux of dextran (4 kDa), compared with the LPS group. Moreover, WPC prevented the LPS-induced decrease (P < 0.05) in claudin-1, occludin and zonula occludens-1 expressions in the jejunal mucosae. WPC also attenuated intestinal inflammation, indicated by decreased (P < 0.05) mRNA expressions of TNF-alpha, IL-6, IL-8 and IL-1 beta. Supplementation with WPC also increased (P < 0.05) TGF-beta 1 protein, phosphorylated-Smad2 expression and Smad4 and Smad7 mRNA expressions and decreased (P< 0.05) the ratios of the phosphorylated to total c-jun N-terminal kinase (JNK) and p38 (phospho-JNK: JNK and p-p38: p38), whereas it increased (P < 0.05) the ratio of extracellular signal-regulated kinase (ERK) (phospho-ERK: ERK). Collectively, these results suggest that dietary inclusion of WPC attenuates the LPS-induced intestinal injury by improving mucosal barrier function, alleviating intestinal inflammation and influencing TGF-beta 1 canonical Smad and mitogen-activated protein kinase signalling pathways.