Gastrointestinal dysfunction induced by early weaning is attenuated by delayed weaning and mast cell blockade in pigs
Gastrointestinal dysfunction induced by early weaning is attenuated by delayed weaning and mast cell blockade in pigs
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DOI：
10.1152/ajpgi.00304.2006
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发表时间：
2007-08-01
影响因子：
4.5
通讯作者：
Blikslager, Anthony T.
中科院分区：
文献类型：
--
作者：
Moeser, Adam J.;Ryan, Kathleen A.;Blikslager, Anthony T.
我们先前的研究表明，19日龄断奶对仔猪肠道黏膜屏障功能有有害影响，这种影响是通过外周促肾上腺皮质激素释放因子（CRF）受体信号通路介导的。本研究的目的是评估仔猪日龄对断奶相关肠道功能障碍的影响，并确定肥大细胞在断奶诱导的黏膜屏障功能破坏中所起的作用。哺乳的约克夏杂交仔猪在19日龄（早期断奶，n = 8）或28日龄（晚期断奶，n = 8）断奶，并饲养在保育栏中。断奶后24小时，采集每个断奶年龄组仔猪的空肠中段和升结肠段，将其安装在尤斯灌流室（Ussing chambers）上，以测量跨上皮电阻和浆膜到黏膜的[³H]甘露醇通量。早期断奶导致空肠和结肠的跨上皮电阻降低，黏膜对[³H]甘露醇的通透性增加（P < 0.01）。相比之下，在28日龄断奶的仔猪中未观察到断奶后肠道屏障功能的降低。与晚期断奶的肠道黏膜相比，早期断奶仔猪的肠道黏膜中CRF受体1蛋白表达增加，黏膜肥大细胞类胰蛋白酶水平升高，且有肥大细胞脱颗粒增强的迹象。在断奶前30分钟腹腔注射肥大细胞稳定剂色甘酸二钠对仔猪进行预处理，可消除早期断奶诱导的肠道屏障紊乱。我们的研究结果表明，早期断奶应激可诱导由肠道肥大细胞激活介导的黏膜功能障碍，并且通过延迟断奶可以预防这种情况。
Our previous work has demonstrated that weaning at 19 days of age has deleterious effects on mucosal barrier function in piglet intestine that are mediated through peripheral CRF receptor signaling pathways. The objectives of the present study were to assess the impact of piglet age on weaning-associated intestinal dysfunction and to determine the role that mast cells play in weaning-induced breakdown of mucosal barrier function. Nursing Yorkshire-cross piglets were either weaned at 19 days of age (early-weaned, n = 8) or 28 days of age (late-weaned, n = 8) and housed in nursery pens. Twenty-four hours postweaning, segments of midjejunum and ascending colon from piglets within each weaning age group were harvested and mounted on Ussing chambers for measurements of trans-epithelial electrical resistance and serosal-to-mucosal [H-3] mannitol fluxes. Early weaning resulted in reductions in transepithelial electrical resistance and increases in mucosal permeability to [H-3] mannitol in the jejunum and colon (P < 0.01). In contrast, postweaning reductions in intestinal barrier function were not observed in piglets weaned at 28 days of age. Early-weaned piglet intestinal mucosa had increased expression of CRF receptor 1 protein, increased mucosal mast cell tryptase levels, and evidence of enhanced mast cell degranulation compared with late-weaned intestinal mucosa. Pretreatment of piglets with the mast cell stabilizer drug cromolyn, injected intraperitoneally 30 min prior to weaning, abolished the early-weaning-induced intestinal barrier disturbances. Our results indicate that early-weaning stress induces mucosal dysfunction mediated by intestinal mast cell activation and can be prevented by delaying weaning.