Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (ChroMetA), KU Leuven, Leuven, Belgium.
Inserm UMR 1073, Institute for Innovation and Biomedical Research, Rouen University, Rouen, France.
Neurogastroenterol Motil. 2019 Jul;31(7):e13614. doi: 10.1111/nmo.13614. Epub 2019 May 8.
A complex interplay between a failing intestinal barrier and low-grade inflammation leading to sensorimotor disturbances is an often-cited mechanism in the pathogenesis of functional gastrointestinal disorders (FGID). However, the cause-consequence relationship between these features has not been clearly established. We previously described jejunal alterations in the normoglycemic BB-rat (BBDP-N) model proposing this model as a suitable animal model to study FGID pathophysiology. The current study explores colonic permeability, inflammation, and sensitivity of the BB-rat.
Colonic tissue of BBDP-N and control (BBDR) rats at 50, 90, 110, 160, and 220 days (n ≥ 7 per group) was used to assess intestinal permeability in Ussing chambers and inflammation, including infiltration by eosinophils, mast cells, and eosinophil peroxidase (EPO) activity. Anxiety-like symptoms were evaluated at 50, 90, and 220 days and colonic sensitivity at 160 and 220 days by measuring the visceromotor response (VMR) to isobaric colorectal distensions.
Lamina propria eosinophil and mast cell infiltration and increased EPO activity were demonstrated from 90 days onward. Increased permeability and myenteric ganglionitis were observed in the oldest BBDP-N rats. At 220 days, the VMR was significantly increased suggesting colonic hypersensitivity. At the same age, increased anxiety-like behavior was observed.
We demonstrated a lamina propria eosinophil and mast cell infiltration preceding visceral hypersensitivity in the colon of the BBDP-N rat, reminiscent of patients with FGID. These findings help elucidating pathogenetic pathways in FGID and further validate the BBDP-N rat as an attractive model to study pathophysiology and therapy of FGID.
在导致感觉运动障碍的功能胃肠病（FGID）发病机制中，肠道屏障功能障碍和低度炎症之间的复杂相互作用常被认为是一个重要机制。然而，这些特征之间的因果关系尚未明确确立。我们之前描述了正常血糖 BB 大鼠（BBDP-N）模型的空肠改变，并提出该模型是研究 FGID 病理生理学的合适动物模型。本研究探讨了 BB 大鼠的结肠通透性、炎症和敏感性。
在 50、90、110、160 和 220 天（每组 n≥7）时，使用 BBDP-N 和对照（BBDR）大鼠的结肠组织在 Ussing 室中评估肠道通透性，并评估炎症，包括嗜酸性粒细胞、肥大细胞浸润和过氧化物酶（EPO）活性。在 50、90 和 220 天时评估焦虑样症状，并在 160 和 220 天时通过测量等压结肠扩张的内脏运动反应（VMR）评估结肠敏感性。
从 90 天开始，显示固有层嗜酸性粒细胞和肥大细胞浸润以及 EPO 活性增加。在最老的 BBDP-N 大鼠中观察到通透性增加和肌间神经节炎。在 220 天时，VMR 显著增加表明结肠高敏感性。在同一年龄，观察到焦虑样行为增加。
我们在 BBDP-N 大鼠的结肠中证明了固有层嗜酸性粒细胞和肥大细胞浸润先于内脏高敏感性，这与 FGID 患者相似。这些发现有助于阐明 FGID 的发病机制，并进一步验证 BBDP-N 大鼠作为研究 FGID 病理生理学和治疗的有吸引力的模型。
