Dietary α-ketoglutarate supplementation ameliorates intestinal injury in lipopolysaccharide-challenged piglets
Dietary α-ketoglutarate supplementation ameliorates intestinal injury in lipopolysaccharide-challenged piglets
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DOI：
10.1007/s00726-010-0473-y
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发表时间：
2010-07-01
期刊：
影响因子：
3.5
通讯作者：
Wu, Guoyao
中科院分区：
文献类型：
--
作者：
Hou, Yongqing;Wang, Lei;Wu, Guoyao
新生儿患炎症性肠病的风险增加，但目前有效的预防和治疗有限。本研究采用脂多糖（LPS）攻击仔猪模型，研究日粮中添加α-酮戊二酸（AKG）对仔猪肠道形态和功能的影响。将18头24日龄猪（21日龄断奶）随机分为对照组、LPS组和LPS + AKG组。对照组和LPS组仔猪饲喂以玉米和豆粕为基础的日粮，而LPS + AKG组饲喂添加1%AKG的基础日粮。在第10、12、14和16天，LPS和LPS + AKG组的仔猪接受腹腔内施用LPS（80 μ g/kg BW），而对照组的仔猪接受相同体积的盐水。在第16天，在LPS或盐水注射后2 h，以0.1g/kg BW的剂量向所有猪口服给予d-木糖，并在此后3 h收集血液样品。给予LPS或盐水后24小时，处死猪以获得肠粘膜用于分析。与对照组相比，LPS刺激可降低十二指肠、空肠和回肠粘膜中蛋白水平、绒毛高度与隐窝深度的比值以及磷酸化mTOR与总mTOR的比值（P < 0.05）。AKG可明显减轻LPS的上述不良反应（P < 0.05）。此外，AKG阻止了LPS诱导的肠HSP 70表达的增加。总的来说，这些新的结果表明，在LPS攻击的仔猪中，膳食补充1%AKG激活mTOR信号传导，减轻粘膜损伤，并改善小肠的吸收功能。这些发现不仅有助于了解AKG在新生儿肠道中的作用模式，而且对炎症条件下的婴儿营养具有重要意义。
Neonates are at increased risk for inflammatory bowel disease, but effective prevention and treatments are currently limited. This study was conducted with the lipopolysaccharide (LPS)-challenged piglet model to determine the effects of dietary supplementation with alpha-ketoglutarate (AKG) on the intestinal morphology and function. Eighteen 24-day-old pigs (weaned at 21 days of age) were assigned randomly to control, LPS, and LPS + AKG groups. The piglets in the control and LPS groups were fed a corn- and soybean meal-based diet, whereas the LPS + AKG group was fed the basal diet supplemented with 1% AKG. On days 10, 12, 14, and 16, piglets in the LPS and LPS + AKG groups received intraperitoneal administration of LPS (80 mu g/kg BW), whereas piglets in the control group received the same volume of saline. On day 16, d-xylose was orally administrated to all pigs at the dose of 0.1 g/kg BW, 2 h after LPS or saline injection, and blood samples were collected 3 h thereafter. Twenty-four hours post-administration of LPS or saline, pigs were killed to obtain intestinal mucosae for analysis. Compared with the control group, LPS challenge reduced (P < 0.05) protein levels, the ratio of villus height to crypt depth, and the ratio of phosphorylated mTOR to total mTOR in duodenal, jejunal, and ileal mucosa. These adverse effects of LPS were attenuated (P < 0.05) by AKG supplementation. Moreover, AKG prevented the LPS-induced increase in intestinal HSP70 expression. Collectively, these novel results indicate that dietary supplementation with 1% AKG activates the mTOR signaling, alleviates the mucosal damage, and improves the absorptive function of the small intestine in LPS-challenged piglets. The findings not only help understand the mode of AKGs actions in the neonatal gut but also have important implications for infant nutrition under inflammatory conditions.