Ekström G M
Dept. of Pharmacology, Preclinical R & D Unit, Astra Draco AB, Lund, Sweden.
Scand J Gastroenterol. 1998 Feb;33(2):174-9. doi: 10.1080/00365529850166914.
The intention of the present study was to develop a new hapten-based inflammatory bowel disease model in the rat, useful for pharmacologic screening of new substances with anti-inflammatory properties and immunomodulating capacities. It was considered important to avoid the use of an irritating barrier breaker, such as ethanol.
Dark Agouti rats were skin-sensitized with oxazolone and further challenged intra-rectally with oxazolone dissolved in carmellose sodium (Orabase)/peanut oil. The effects of treatment with budesonide, prednisolone, cyclosporin A, and 5-aminosalicylic acid (5-ASA) were studied.
The intra-rectal challenge with oxazolone in sensitized rats induced an inflammation with an increased colon wet weight, pronounced myeloperoxidase (MPO) activity, and hyperemia/ulcerations in the epithelial lining. Improvement was achieved by treatment with budesonide, prednisolone, and cyclosporin A but not with 5-ASA.
The model fulfills the criteria for a fast, reproducible animal model for human colon inflammation, suitable for pharmacologic screening and studies of an immune-driven colon inflammation.
本研究的目的是在大鼠中建立一种基于新半抗原的炎症性肠病模型，用于对具有抗炎特性和免疫调节能力的新物质进行药理学筛选。避免使用刺激性屏障破坏剂（如乙醇）被认为很重要。
用恶唑酮对深色刺鼠进行皮肤致敏，然后用溶解于羧甲基纤维素钠（Orabase）/花生油中的恶唑酮经直肠再次激发。研究了布地奈德、泼尼松龙、环孢素A和5-氨基水杨酸（5-ASA）的治疗效果。
致敏大鼠经直肠给予恶唑酮激发后引发炎症，表现为结肠湿重增加、髓过氧化物酶（MPO）活性明显升高以及上皮层充血/溃疡。布地奈德、泼尼松龙和环孢素A治疗可改善病情，但5-ASA治疗无效。
该模型符合快速、可重复的人类结肠炎症动物模型标准，适用于药理学筛选和免疫驱动的结肠炎症研究。
