Early weaning stress impairs development of mucosal barrier function in the porcine intestine
Early weaning stress impairs development of mucosal barrier function in the porcine intestine
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DOI：
10.1152/ajpgi.00081.2009
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发表时间：
2010-03-01
影响因子：
4.5
通讯作者：
Moeser, Adam J.
中科院分区：
文献类型：
--
作者：
Smith, Feli;Clark, Jessica E.;Moeser, Adam J.
Smith F，Clark JE，Overman BL，Tozel CC，Huang JH，Rivier JE，Blisklager AT，Moeser AJ.早期断奶应激损害猪肠粘膜屏障功能的发育。美国生理学杂志胃肠和肝脏生理学298：G352-G363，2010。首次发表于2009年11月19日; doi：10.1152/ajpgi.00081.2009。早期生活压力是成年后慢性肠道疾病发展的诱发因素。在这里，我们表明，压力与早期断奶猪导致粘膜屏障功能受损。早期断奶（断奶日龄15- 21天）导致肠屏障功能持续受损，如在5周龄和9周龄时测量的空肠跨上皮电阻降低和粘膜-浆膜旁探针[H-3]甘露醇和[C-14]菊粉通量升高所示，与晚断奶猪（断奶日龄23- 28天）相比。在早期断奶仔猪的空肠中观察到基线短路电流升高，并显示通过增强Cl-分泌介导。早期断奶仔猪空肠屏障功能障碍与固有层免疫细胞密度增加，特别是粘膜肥大细胞密度增加一致。肥大细胞稳定剂色甘酸钠可改善早期断奶仔猪的屏障功能障碍和分泌过多，表明肥大细胞的重要作用。此外，激活肥大细胞离体与c48/80和促肾上腺皮质激素释放因子（CRF）在猪空肠安装在Ussing室诱导屏障功能障碍和升高的短路电流，抑制肥大细胞蛋白酶抑制剂。选择性CRF受体拮抗剂给药早期断奶猪的实验表明，CRF受体1（CRFr 1）激活介导屏障功能障碍和分泌过多，而CRFr 2激活可能是负责新的保护性能在猪肠响应生命早期的压力。
Smith F, Clark JE, Overman BL, Tozel CC, Huang JH, Rivier JE, Blisklager AT, Moeser AJ. Early weaning stress impairs development of mucosal barrier function in the porcine intestine. Am J Physiol Gastrointest Liver Physiol 298: G352-G363, 2010. First published November 19, 2009; doi: 10.1152/ajpgi.00081.2009.-Early life stress is a predisposing factor for the development of chronic intestinal disorders in adult life. Here, we show that stress associated with early weaning in pigs leads to impaired mucosal barrier function. Early weaning (15- to 21-day weaning age) resulted in sustained impairment in intestinal barrier function, as indicated by reductions in jejunal transepithelial electrical resistance and elevations in mucosal-to-serosal flux of paracellular probes [H-3] mannitol and [C-14] inulin measured at 5 and 9 wk of age, compared with that shown in late-weaned pigs (23- to 28-day weaning age). Elevated baseline short-circuit current was observed in jejunum from early-weaned pigs and was shown to be mediated via enhanced Cl- secretion. Jejunal barrier dysfunction in early-weaned pigs coincided with increased lamina propria immune cell density particularly mucosal mast cells. The mast cell stabilizer drug sodium cromoglycolate ameliorated barrier dysfunction and hypersecretion in early-weaned pigs, demonstrating an important role of mast cells. Furthermore, activation of mast cells ex vivo with c48/80 and corticotrophin-releasing factor (CRF) in pig jejunum mounted in Ussing chambers induced barrier dysfunction and elevations in short-circuit current that were inhibited with mast cell protease inhibitors. Experiments in which selective CRF receptor antagonists were administered to early-weaned pigs revealed that CRF receptor 1 (CRFr1) activation mediates barrier dysfunction and hypersecretion, whereas CRFr2 activation may be responsible for novel protective properties in the porcine intestine in response to early life stress.