Neonatal maternal deprivation triggers long term alterations in colonic epithelial barrier and mucosal immunity in rats
Neonatal maternal deprivation triggers long term alterations in colonic epithelial barrier and mucosal immunity in rats
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DOI：
10.1136/gut.2003.024174
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发表时间：
2004-04-01
期刊：
影响因子：
24.5
通讯作者：
Bueno, L
中科院分区：
文献类型：
--
作者：
Barreau, F;Ferrier, L;Bueno, L
背景：生命早期的应激事件（例如，母性剥夺）已被证明会改变成人的免疫和胃肠道功能。本研究旨在确定母性剥夺是否影响成年大鼠结肠上皮屏障和实验性结肠炎的发生。方法：雄性Wistar大鼠仔仔在出生后2 ~ 14天分离或不受干扰。在12周龄时，我们评估了结肠细胞旁通透性、细菌易位、髓过氧化物酶（MPO）活性、粘膜肥大细胞密度、细胞因子(白细胞介素（IL)-1 β、IL-2、IL-4、IL-10和干扰素γ (ifn - γ)） mRNA表达和宏观损伤。在结肠内给药2,4,6-三硝基苯磺酸（TNBS） 4天后，还评估了总肠道通透性、MPO活性和宏观损伤。结果：母体剥夺引发结肠通透性显著增加，与细菌易位进入肠系膜淋巴结、肝脏和脾脏有关。这些改变与一些宏观损伤、结肠MPO活性、粘膜肥大细胞密度和细胞因子mRNA表达的增加有关。通过增强MPO结肠水平、肠道总通透性和宏观病变来判断，在分离的动物中，结肠内输注TNBS诱导的炎症反应明显升高。结论：母体剥夺促进结肠上皮屏障的长期改变，这与对外部免疫刺激的过度免疫反应有关。这表明早期心理因素在晚年结肠粘膜屏障的调节中起作用。
Background: Stressful events in the early period of life ( for example, maternal deprivation) have been shown to modify adult immune and gastrointestinal tract functions. The present study aimed to establish whether maternal deprivation affects colonic epithelial barrier and the development of an experimental colitis in adult rats.Methods: Male Wistar rat pups were separated during postnatal days 2 - 14 or left undisturbed with their dam. At 12 weeks of age, we assessed colonic paracellular permeability, bacterial translocation, myeloperoxidase (MPO) activity, mucosal mast cell density, cytokine (interleukin (IL)-1beta, IL-2, IL-4, IL-10, and interferon gamma (IFN-gamma)) mRNA expression, and macroscopic damage. Total gut permeability, MPO activity, and macroscopic damage were also assessed four days after intracolonic administration of 2,4,6-trinitrobenzenesulphonic acid (TNBS).Results: Maternal deprivation triggered a significant increase in colonic permeability associated with bacterial translocation into the mesenteric lymph nodes, liver, and spleen. These alterations were associated with some macroscopic damage and an increase in colonic MPO activity, mucosal mast cell density, and cytokine mRNA expression. Intracolonic infusion of TNBS induced a significantly higher inflammatory reaction in separated animals, as judged by enhanced MPO colonic levels, total gut permeability, and macroscopic lesions.Conclusions: Maternal deprivation promotes long term alterations in the colonic epithelial barrier associated with an exaggerated immune response to an external immune stimulus. This suggests a role for early psychological factors in the regulation of colonic mucosal barrier in later life.