Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.
J Pediatr Gastroenterol Nutr. 2010 Mar;50(3):240-50. doi: 10.1097/MPG.0b013e3181cb8f4a.
: Chronic models of inflammatory bowel disease are lacking in preadult rodents. The primary goal of our study was to develop a chronic model of hapten-induced intestinal inflammation and fibrosis in young rats. Second, we aimed to determine the profiles of key Th-1, Th-2, and Th-17 proinflammatory and profibrotic cytokines, during the progression of colitis in young rats.
Chronic hapten-induced colitis was induced by the administration of intracolonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) in young Wistar rats (postnatal days 23, 35, 48, and 59). After 1, 3, or 4 cycles of TNBS, rats were euthanized and the colons were removed for the measurement of macroscopic, histologic, and biochemical parameters of colitis.
Young rats developed moderate to severe colitis in the distal colon, without significant morbidity or mortality. Macroscopic severity, histologic pathology, and colonic weights increased progressively with repeated TNBS administration. Cobblestone-like ulceration and fibrosis was evident in the colon, particularly after 4 cycles of TNBS. There was a unique cytokine pattern associated with colitis in young rats. Interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha peaked during the earlier postnatal time points (days 28 and 54) and then declined after repetitive administration of the hapten (day 67). In contrast, IL-13 and IL-17 were consistently elevated after administration of TNBS to the colon of young rats.
A new model of colitis was established in young rats, which has a unique pattern of Th-1, Th-2, and Th-17 cytokine induction. This chronic TNBS model may be useful for studying the development of inflammation and fibrosis in preadult animals.
幼年啮齿动物缺乏慢性炎症性肠病模型。我们的主要目标是建立一种幼鼠半抗原诱导的肠道炎症和纤维化的慢性模型。其次，我们旨在确定幼鼠结肠炎进展过程中关键 Th1、Th2 和 Th17 促炎和促纤维化细胞因子的特征。
通过在幼年 Wistar 大鼠（出生后第 23、35、48 和 59 天）的结肠内给予 2,4,6-三硝基苯磺酸（TNBS）诱导慢性半抗原诱导的结肠炎。在接受 1、3 或 4 个 TNBS 循环后，处死大鼠并取出结肠，用于测量结肠炎的宏观、组织学和生化参数。
幼鼠在远端结肠中发生中度至重度结肠炎，无明显发病率或死亡率。随着 TNBS 重复给药，宏观严重程度、组织病理学和结肠重量逐渐增加。在结肠中可见鹅卵石样溃疡和纤维化，尤其是在接受 4 个 TNBS 周期后。幼鼠结肠炎与独特的细胞因子模式相关。白细胞介素（IL）-12 和肿瘤坏死因子（TNF）-α在出生后早期时间点（第 28 天和第 54 天）达到峰值，然后在反复给予半抗原后下降（第 67 天）。相比之下，IL-13 和 IL-17 在 TNBS 给药后持续升高。
在幼鼠中建立了一种新的结肠炎模型，其具有独特的 Th1、Th2 和 Th17 细胞因子诱导模式。这种慢性 TNBS 模型可能有助于研究未成年动物中炎症和纤维化的发展。
