Repeated measurement of intestinal permeability as an assessment of colitis severity in HLA-B27 transgenic rats

作     者：Kerr, SW Wolyniec, WW Filipovic, Z Nodop, SG Braza, F Winquist, RJ Noonan, TC 

作者机构：Boehringer Ingelheim Pharmaceut Inc Dept Pharmacol Ctr Res & Dev Ridgefield CT 06877 USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第291卷第2期

页      面：903-910页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

主　　题：生物学标记 结肠炎/诊断 结肠/病理学 造影剂/药代动力学 环孢菌素/治疗应用 剂量效应关系 药物 药物相互作用 粪便/化学 HLA-B27抗原/遗传学 炎症/病理学 肠黏膜/代谢 白细胞 单核/生理学 器官测量 通透性 大鼠 近交F344 大鼠 突变系 柳氮磺胺吡啶/治疗应用 时间因素 三碘苯甲酸类/药代动力学 动物 人类 男(雄)性 大鼠 

摘      要：We report on the development of a method for repeated monitoring of mucosal permeability that allows assessment of the severity of colitis and evaluation of treatment efficacy in HLA-B27 transgenic rats. We determined the extent to which intestinal permeability related to stool condition, colon weight, and histological pathology in precolitic and diseased rats up to 29 weeks old. Intestinal permeability was measured by the urinary excretion of iodixanol at 24 h after oral administration. Mean permeability values increased significantly with age in HLA-B27 rats but remained decreased in the background strain Fischer-344 (F-344) control animals. Macroscopic evaluation of HLA-B27 rat colons between 20 and 24 weeks old showed colonic thickening with colonic wet weights increased from 3.4 +/- 0.13 mg/kg ***. in F-344 rats to 6.79 +/- 0.73 mg/kg ***. (p.05) in HLA-B27 rats. Histological examination of HLA-B27 rat colons confirmed the colonic inflammation as a chronic active mononuclear cell infiltrate. The increase in colon weight was associated with an increase in permeability: 1.16 +/- 0.17 mg iodixanol versus 5.37 +/- 1.3 mg of iodixanol in F-344 and HLA-B27 rats, respectively. Three weeks treatment of HLA-B27 rats with cyclosporin A, but not sulfasalazine, showed a dose-dependent decrease in mucosal permeability and colon weight. Neither treatment improved stool condition. We conclude that the measurement of intestinal permeability by iodixanol excretion is a useful biochemical marker that is associated with increases in colonic weight and histological evaluation of inflammation. These data indicate that this technique may be valuable for diagnostic and evaluation purposes in preclinical models of inflammatory bowel disease.