大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右

A chronic ulcerative colitis model in the rat

AIM To evaluate the effect of trinitrobenzenesulfonic acid (TNBS) at various concentration on colonic damage in rats. METHODS A chronic inflammation of the rat colon was induced by a single colonic instillation of TNBS(25～150 mg·kg -1 )dissolved in 0.5 ml of 30% ethanol. Three weeks after exposure to TNBS, the severity of colonic damage were assessed by gross appearance using a grading scale (0～5), colon weights and by histology. The number of neutrophils present in inflammed colonic tissue was quantitated by the myeloperoxidase (MPO) assay. The relationship between MPO activity and time course was studied. RESULTS At a dose of 100～150 mg·kg -1 ,TNBS/ethanol induced ulceration and marked thicking of the bowel wall persisted for at least 7 wk, a significant increase in MPO activity . Histologically, the inflammatory response induced mucosal and submucosal infiltration by neutrophils, macrophages, lymphocytes and fibroblasts, granulomas formation and cryptoabscess was also obsevered. At TNBS dose of 50 mg·kg -1 there was a lower level of colonic damage, the lowest dose of TNBS(25 mg·kg -1 ) had damage scores, colon weights, and tissue levels of MPO activity that were not significantly different from control animals ( P >0.05) CONCLUSION The characteristics and relatively long duration of ulceration and inflammation induced in this model afford an opportunity to evaluate treatments drug applicable to inflammatory bowel disease in humans. A TNBS dose of 100 mg·kg -1 was chosen for an appropriate experimental dose.