Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Neurogastroenterol Motil. 2013 Feb;25(2):e127-39. doi: 10.1111/nmo.12066.
Chronic psychological stress (CPS) is associated with increased intestinal epithelial permeability and visceral hyperalgesia. It is unknown whether corticosterone (CORT) plays a role in mediating alterations of epithelial permeability in response to CPS.
Male rats were subjected to 1-h water avoidance (WA) stress or subcutaneous CORT injection daily for 10 consecutive days in the presence or absence of corticoid receptor antagonist RU-486. The visceromotor response (VMR) to colorectal distension (CRD) was measured. The in situ single-pass intestinal perfusion was used to measure intestinal permeability in jejunum and colon simultaneously.
We observed significant decreases in the levels of glucocorticoid receptor (GR) and tight junction proteins in the colon, but not the jejunum in stressed rats. These changes were largely reproduced by serial CORT injections in control rats and were significantly reversed by RU-486. Stressed and CORT-injected rats demonstrated a threefold increase in permeability for PEG-400 (MW) in colon, but not jejunum and significant increase in VMR to CRD, which was significantly reversed by RU-486. In addition, no differences in permeability to PEG-4000 and PEG-35 000 were detected between control and WA groups.
CONCLUSIONS & INFERENCES: Our findings indicate that CPS was associated with region-specific decrease in epithelial tight junction protein levels in the colon, increased colon epithelial permeability to low molecular weight macromolecules which were largely reproduced by CORT treatment in control rats and prevented by RU-486. These observations implicate a novel, region-specific role for CORT as a mediator of CPS-induced increased permeability to macromolecules across the colon epithelium.
慢性心理应激（CPS）与肠上皮通透性增加和内脏痛觉过敏有关。皮质酮（CORT）是否在介导 CPS 引起的上皮通透性改变中起作用尚不清楚。
雄性大鼠连续 10 天每天接受 1 小时的水回避（WA）应激或皮下 CORT 注射，同时存在或不存在皮质激素受体拮抗剂 RU-486。测量对结直肠扩张（CRD）的内脏运动反应（VMR）。原位单次肠灌注同时测量空肠和结肠的肠通透性。
我们观察到应激大鼠结肠中糖皮质激素受体（GR）和紧密连接蛋白水平显著降低，但空肠无此变化。这些变化在对照大鼠的连续 CORT 注射中得到了很大程度的重现，并且被 RU-486 显著逆转。应激和 CORT 注射大鼠的结肠对 PEG-400（MW）的通透性增加了三倍，但空肠和 CRD 的 VMR 显著增加，这被 RU-486 显著逆转。此外，对照和 WA 组之间对 PEG-4000 和 PEG-35000 的通透性没有差异。
我们的研究结果表明，CPS 与结肠上皮紧密连接蛋白水平的区域特异性降低有关，增加了低分子量大分子穿过结肠上皮的通透性，这些变化在对照大鼠的 CORT 处理中得到了很大程度的重现，并被 RU-486 所预防。这些观察结果表明 CORT 作为 CPS 引起的大分子跨结肠上皮通透性增加的介质具有新的、区域特异性的作用。
