Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景:大量小鼠模型被用于模拟和研究肠道炎症。T细胞受体α链（TCRα）缺陷型小鼠用作自发性结肠炎的模型，与人溃疡性结肠炎具有相似性。然而,结肠炎在小鼠的生命后期触发（年龄：4-5个月），在不同的小鼠中，炎症不会同时发生。先前进行的一项研究报道，吡罗昔康的给药在6-8周龄的TCRα缺陷小鼠中引发了可预测的早期结肠炎。然而,未提供后续炎症的详细表征.
方法：我们在TCRα缺陷小鼠中对吡罗昔康触发的结肠炎进行了深入检查，重点是空间组织病理学变化和炎症标志物表达的分析。此外，我们测试了地塞米松对结肠炎的改善作用.
结果：我们证实吡罗昔康诱导了定时结肠炎，并且在TCRα缺陷小鼠的近端结肠和盲肠中也是如此。观察到吡罗昔康给药诱导上皮增生，杯状细胞丢失,白细胞浸润，偶有溃疡。使用瑞士滚动技术检查整个结肠和盲肠。重要的是,我们观察到炎症是多灶性节段，在健康组织之间的组织损伤区域。此外,我们观察到重复动物和治疗中炎症严重程度的差异，地塞米松的给药只能部分改善近端结肠的炎症。
结论：吡罗昔康持续诱导近端结肠和盲肠多灶性节段性结肠炎，尽管后者的炎症程度有所减轻。重要的是,在使用这种小鼠同步性结肠炎模型时,必须考虑大肠炎症的空间变异性和炎症严重程度的重复间差异.
方法：我们在TCRα缺陷小鼠中对吡罗昔康触发的结肠炎进行了深入检查，重点是空间组织病理学变化和炎症标志物表达的分析。此外，我们测试了地塞米松对结肠炎的改善作用.
结果：我们证实吡罗昔康诱导了定时结肠炎，并且在TCRα缺陷小鼠的近端结肠和盲肠中也是如此。观察到吡罗昔康给药诱导上皮增生，杯状细胞丢失,白细胞浸润，偶有溃疡。使用瑞士滚动技术检查整个结肠和盲肠。重要的是,我们观察到炎症是多灶性节段，在健康组织之间的组织损伤区域。此外,我们观察到重复动物和治疗中炎症严重程度的差异，地塞米松的给药只能部分改善近端结肠的炎症。
结论：吡罗昔康持续诱导近端结肠和盲肠多灶性节段性结肠炎，尽管后者的炎症程度有所减轻。重要的是,在使用这种小鼠同步性结肠炎模型时,必须考虑大肠炎症的空间变异性和炎症严重程度的重复间差异.
