Chronic psychological stress in rats induces intestinal sensitization to luminal antigens
Chronic psychological stress in rats induces intestinal sensitization to luminal antigens
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DOI：
10.2353/ajpath.2006.050575
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发表时间：
2006-01-01
影响因子：
6
通讯作者：
Perdue, MH
中科院分区：
文献类型：
--
作者：
Yang, PC;Jury, J;Perdue, MH
越来越多的证据表明，应激在慢性肠道疾病的病理生理中起作用，但其机制尚不清楚。先前对大鼠的研究表明，压力会降低肠道屏障功能，并允许过度吸收肠道物质。在这里，我们研究了慢性心理应激是否会诱导肠道组织对口腔抗原的致敏。大鼠每天进行1小时的避水应激或模拟应激，连续10天，第5天灌胃给予辣根过氧化物酶（HRP）。在第20天进行致敏性研究。所有应激大鼠均出现hrp特异性IgE抗体，抗原诱导肠道分泌，肠道黏膜炎症细胞数量增加。肠细胞更容易吸收腔内HRP；压力大的动物。此外，应激大鼠在肠道inucosa中白细胞介素-4的表达增加，干扰素- γ的表达减少，这是一种典型的过敏条件的细胞因子谱。用促肾上腺皮质激素释放激素拮抗剂（先前显示可抑制应激增强的肠道通透性）治疗应激大鼠，消除了肠道过敏的表现。我们的研究结果表明，慢性心理应激期间口服抗原的存在改变了免疫反应（致敏而不是口服耐受），并导致随后抗原诱导的肠道病理生理。
There is increasing evidence that stress plays a role in the pathophysiology of chronic intestinal disorders, but the mechanisms remain unclear. Previous studies in rats have revealed that stress decreases gut barrier function and allows excessive uptake of luminal material. Here, we investigated whether chronic psychological stress acts to induce sensitization of intestinal tissues to oral antigens. Rats were subjected to 1 hour per day of water avoidance stress or sham stress daily for 10 days, and horseradish peroxidase (HRP) was delivered by gavage on day 5. Studies to determine sensitization were conducted on day 20. All stressed rats developed HRP-specific IgE antibodies, antigen-induced intestinal secretion, and increased numbers of inflammatory cells in gut mucosa. Luminal HRP was absorbed more readily by enterocytes; of stressed animals. in addition, stressed rats had increased expression of interleukin-4 and decreased expression of interferon-gamma in gut inucosa, a cytokine profile that is typical of allergic conditions. Treatment of stressed rats with an antagonist to corticotropin-releasing hormone (previously shown to inhibit stress-enhanced gut permeability) eliminated the manifestations of intestinal hypersensitivity. Our results indicate that the presence of oral antigen during chronic psychological stress alters the immune response (to sensitization rather than oral tolerance) and causes subsequent antigen-induced gut pathophysiology.