Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, Alberta, Canada.
Alberta Health Services, Chinook Regional Hospital, Lethbridge, Alberta, Canada.
Animal Model Exp Med. 2024 Aug;7(4):533-543. doi: 10.1002/ame2.12456. Epub 2024 Jul 11.
A multitude of mouse models are utilized to emulate and study intestinal inflammation. T-cell receptor alpha chain (TCRα)-deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative colitis. However, colitis is triggered late in the life of the mouse (age: 4-5 months), and inflammation does not develop at the same time in different mice. A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα-deficient mice at the age of 6-8 weeks. However, a detailed characterization of ensuing inflammation was not provided.
We conducted an in-depth examination of piroxicam-triggered colitis in TCRα-deficient mice, with emphasis on spatial histopathologic changes and analysis of expression of inflammatory markers. Furthermore, we tested amelioration of colitis with dexamethasone.
We confirmed that piroxicam induced a time-prescribed colitis and did so in the proximal colon as well as the cecum of TCRα-deficient mice. Piroxicam administration was observed to induce epithelial hyperplasia, goblet cell loss, and leukocyte infiltration with occasional ulceration. A Swiss roll technique was used to examine the colon and cecum in its entirety. Importantly, we observed that inflammation was multifocal segmental, with areas of tissue damage in between healthy tissue. In addition, we observed variability in the severity of inflammation among replicate animals and treatments, and that the administration of dexamethasone only partially ameliorated inflammation in the proximal colon.
Piroxicam consistently induced multifocal segmental colitis in the proximal colon and cecum, although the degree of inflammation was reduced in the latter. Importantly, spatial variability in inflammation in the large intestine and the inter-replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis.
大量的小鼠模型被用于模拟和研究肠道炎症。T 细胞受体α链（TCRα）缺陷小鼠被用作自发性结肠炎的模型，其与人类溃疡性结肠炎具有相似性。然而，这种结肠炎在小鼠生命的后期才会发作（年龄：4-5 个月），而且不同小鼠的炎症不会同时发作。先前的一项研究报告称，在 6-8 周龄时，给 TCRα 缺陷小鼠施用吡罗昔康会引发可预测的早期结肠炎。然而，并没有提供对随后炎症的详细描述。
我们对 TCRα 缺陷小鼠的吡罗昔康诱导结肠炎进行了深入研究，重点关注空间组织病理学变化和炎症标志物的表达分析。此外，我们还测试了地塞米松对结肠炎的改善作用。
我们证实吡罗昔康诱导了一种时间规定的结肠炎，并且在 TCRα 缺陷小鼠的近端结肠和盲肠中均如此。吡罗昔康给药导致上皮细胞增生、杯状细胞丢失和白细胞浸润，偶尔出现溃疡。我们使用瑞士卷技术对整个结肠和盲肠进行了检查。重要的是，我们观察到炎症是多灶性节段性的，在健康组织之间存在组织损伤区域。此外，我们观察到在复制动物和处理之间，炎症的严重程度存在差异，并且地塞米松的给药仅部分改善了近端结肠的炎症。
吡罗昔康在近端结肠和盲肠中一致地诱导多灶性节段性结肠炎，尽管后者的炎症程度降低。重要的是，在利用这种同步结肠炎的小鼠模型时，必须考虑到大肠炎症的空间变异性和炎症严重程度的复制间变异性。
