Clapp N, Henke M, Hansard R, Carson R, Walsh R, Widomski D, Anglin C, Fretland D
Marmoset Research Center, Oak Ridge (MARCOR), Oak Ridge Associated Universities, TN.
Agents Actions. 1993;39 Spec No:C8-10. doi: 10.1007/BF01972704.
Use of the CTT model provides insight into the inflammatory mediator contribution in the pathogenesis of idiopathic colitis. To evaluate anti-colitic efficacy, the leukotriene B4 receptor antagonist and anti-inflammatory agent, SC-41930, was administered (10 mg/kg BW by gavage BID) for 8 weeks to CTTs with histologically confirmed persistent and defined active colitis. The inflammatory mediators LTB4, PGE2, TXB2, and PAF were assayed in colonic dialysate that was collected after 1 1/2 h from four CTTs pre-, mid-, and post-treatment, frozen at -70 degrees C, and analyzed by RIA after HPLC purification. LTB4 levels were lower at mid- and post-treatment and had little inter-animal variation post-treatment. PGE2 and PAF levels were elevated during SC-41930 treatment, but there was a trend towards lower thromboxane B2 levels. Reduced LTB4 (PMN degranulation and chemotaxis) and increased PGE2 (mucosal-protective effect) may, in part, explain the observed efficacy of SC-41930 in active tamarin colitis.
使用CTT模型有助于深入了解炎症介质在特发性结肠炎发病机制中的作用。为评估抗结肠炎疗效，对白喉毒素处理的恒河猴（CTT）（经组织学确认患有持续性和明确的活动性结肠炎）给予白三烯B4受体拮抗剂和抗炎药SC-41930（按体重10mg/kg灌胃，每日两次），持续8周。在治疗前、治疗中期和治疗后1.5小时，从四只CTT收集结肠透析液，测定其中的炎症介质白三烯B4（LTB4）、前列腺素E2（PGE2）、血栓素B2（TXB2）和血小板活化因子（PAF），将其在-70℃冷冻，经高效液相色谱（HPLC）纯化后采用放射免疫分析法（RIA）进行分析。治疗中期和治疗后LTB4水平降低，且治疗后动物间差异较小。在SC-41930治疗期间，PGE2和PAF水平升高，但血栓素B2水平有降低趋势。LTB4减少（中性粒细胞脱颗粒和趋化作用）和PGE2增加（黏膜保护作用）可能部分解释了SC-41930在活动性绢毛猴结肠炎中观察到的疗效。
