Lauffer Adriana, Vanuytsel Tim, Vanormelingen Christophe, Vanheel Hanne, Salim Rasoel Shadea, Tóth Joran, Tack Jan, Fornari Fernando, Farré Ricard
a Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven , Leuven , Belgium .
b Programa De Pós-Graduação: Ciências Em Gastroenterologia E Hepatologia, Faculdade De Medicina, UFRGS , Porto Alegre , Brazil , and.
Stress. 2016;19(2):225-34. doi: 10.3109/10253890.2016.1154527. Epub 2016 Mar 7.
Psychological stress increases intestinal permeability, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders. We assessed the effect of subacute, chronic and combined stress on intestinal barrier function and mast cell density. Male Wistar rats were allocated to four experimental groups (n = 8/group): 1/sham; 2/subacute stress (isolation and limited movement for 24 h); 3/chronic crowding stress for 14 days and 4/combined subacute and chronic stress. Jejunum and colon were collected to measure: transepithelial electrical resistance (TEER; a measure of epithelial barrier function); gene expression of tight junction molecules; mast cell density. Plasma corticosterone concentration was increased in all three stress conditions versus sham, with highest concentrations in the combined stress condition. TEER in the jejunum was decreased in all stress conditions, but was significantly lower in the combined stress condition than in the other groups. TEER in the jejunum correlated negatively with corticosterone concentration. Increased expression of claudin 1, 5 and 8, occludin and zonula occludens 1 mRNAs was detected after subacute stress in the jejunum. In contrast, colonic TEER was decreased only after combined stress, and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the chronic and combined stress condition in the colon only. In conclusion, our data show that chronic stress sensitizes the gastrointestinal tract to the effects of subacute stress on intestinal barrier function; different underlying cellular and molecular alterations are indicated in the small intestine versus the colon.
心理应激会增加肠道通透性，可能导致功能性胃肠疾病中的低度炎症和症状。我们评估了亚急性、慢性和联合应激对肠道屏障功能和肥大细胞密度的影响。将雄性Wistar大鼠分为四个实验组（每组n = 8）：1/假手术组；2/亚急性应激组（隔离并限制活动24小时）；3/慢性拥挤应激组，持续14天；4/亚急性和慢性联合应激组。收集空肠和结肠以测量：跨上皮电阻（TEER；上皮屏障功能的指标）；紧密连接分子的基因表达；肥大细胞密度。与假手术组相比，在所有三种应激条件下血浆皮质酮浓度均升高，在联合应激条件下浓度最高。在所有应激条件下空肠的TEER均降低，但联合应激条件下显著低于其他组。空肠的TEER与皮质酮浓度呈负相关。亚急性应激后空肠中检测到claudin 1、5和8、闭合蛋白和闭合小带1 mRNA的表达增加。相反，仅在联合应激后结肠TEER降低，紧密连接分子的表达未改变。仅在结肠的慢性和联合应激条件下观察到肥大细胞密度增加。总之，我们的数据表明，慢性应激使胃肠道对亚急性应激对肠道屏障功能的影响敏感；小肠和结肠中存在不同的潜在细胞和分子改变。
