Administration of alpha-ketoglutarate improves epithelial restitution under stress injury in early-weaning piglets.
Administration of alpha-ketoglutarate improves epithelial restitution under stress injury in early-weaning piglets.
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给予α-酮戊二酸可改善早期断奶仔猪应激损伤下的上皮恢复
DOI：
10.18632/oncotarget.20555
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发表时间：
2017-11-03
期刊：
影响因子：
--
通讯作者：
Yin Y
中科院分区：
文献类型：
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作者：
He L;Zhou X;Huang N;Li H;Cui Z;Tian J;Jiang Q;Liu S;Wu J;Li T;Yao K;Yin Y
α-酮戊二酸（AKG）是一种重要的细胞代谢产物，参与能量产生和氨基酸代谢。然而，AKG对粘膜损伤的保护作用及其机制尚不清楚。本研究旨在研究日粮中添加AKG对大肠杆菌脂多糖（LPS）诱导的早期断奶仔猪上皮修复的影响。试验采用2 × 2析因设计，试验因素为基础日粮（基础日粮或AKG日粮）和炎症刺激（LPS或生理盐水）。结果表明，添加AKG可改善LPS诱导的早期断奶仔猪的生长性能和肠道形态。与基础日粮相比，AKG日粮显著降低了LPS诱导仔猪肠道炎性细胞因子（IL-1β、IL-6和IL-12）的浓度和mRNA表达。此外，AKG给药上调了生理盐水和LPS处理仔猪小肠中营养敏感转运蛋白（GLUT-2、SGLT-1、PEPT-1、I-FABP 2）的mRNA表达，并改善了紧密连接基因和蛋白（ZO-1、Occludin、Claudins、E-cadherin）的分布和表达。综上所述，AKG具有减轻早期断奶仔猪应激损伤后肠道炎症反应、促进肠上皮修复和营养感受能力的潜力，为AKG在猪生产中的肠内应用和临床应用提供了实验依据。
Alpha-ketoglutarate (AKG) is an important cellular metabolite that participates in energy production and amino acid metabolism. However, the protective effects and mechanism of AKG on mucosal lesions have not been well understood. This study was conducted to investigate the effects of dietary AKG supplementation on epithelial restitution in early-weaning piglets under Escherichia coli lipopolysaccharide (LPS) induction. A total of 32 weaned piglets were used in a 2 × 2 factorial design; the major factors were dietary treatment (basal diet or AKG diet) and inflammatory challenge (LPS or saline). The results showed that AKG supplementation improved the growth performance and intestinal morphology in the LPS-induced early-weaning piglets. Compared with the basal diet, the AKG diet remarkably decreased the concentration and mRNA expression of intestinal inflammatory cytokines (IL-1β, IL-6, and IL-12) in the LPS-induced piglets. Moreover, AKG administration upregulated the mRNA expression of nutrient-sensing transporters (GLUT-2, SGLT-1, PEPT-1, I-FABP2) in the small intestine of both saline- and LPS-treated piglets, and improved the distribution and expression of tight-junction genes andproteins (ZO-1, Occludin, Claudins, E-cadherin). Collectively, our findings indicate that AKG has the potential to alleviate intestinal inflammatory response and improve epithelial restitution and nutrient-sensing ability under stress injury in early-weaning piglets, and it also provides an experimental basis for enteral use of AKG in swine production and clinical application to prevent intestinal epithelial damage.