Carvalho C, Jancar S, Sirois P
Department of Pharmacology, Medical School, University of Sherbrooke, QC, Canada.
Can J Physiol Pharmacol. 1998 Jul-Aug;76(7-8):715-20. doi: 10.1139/cjpp-76-7-8-715.
Sensitized guinea pigs were used to assess the effect of treatment with the compound U-83836E ((-)-2-[[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]methyl]-3 ,4-dihydro-2,5,7,8-tetramethyl-2H--benzopyran-6-ol, dihydrochloride) on the antigen-induced late-phase (16 h) airway hyperreactivity, increase in inflammatory cell number, edema, and release of inflammatory mediators in the bronchoalveolar lavage (BAL) fluid. After antigen challenge, an increase of the in vitro reactivity of the trachea and upper bronchi to acetylcholine and histamine and an increase in the number of leukocytes in the BAL fluid, mainly eosinophils and mononuclear cells, were observed. The concentrations of proteins, histamine, and PGE2 in the BAL fluid were also significantly increased by 53, 57, and 216%, respectively, after antigen challenge. Treatment with U-83836E (10 mg/kg) given i.p. 17 and 3 h before and 6 h after antigen challenge inhibited by approximately 80% the total cell number in the airways and the BAL fluid protein content. Moreover, this treatment totally inhibited airway hyperreactivity. Histamine and PGE2 levels in the BAL fluid were not significantly affected by U-83836E treatment. These results indicate that U-83836E is effective against some of the characteristic features of asthma in ovalbumin-sensitized guinea pigs.
使用致敏豚鼠评估化合物U - 83836E（（-）-2 - [[4 - （2,6 - 二 - 1 - 吡咯烷基 - 4 - 嘧啶基）-1 - 哌嗪基]甲基] - 3,4 - 二氢 - 2,5,7,8 - 四甲基 - 2H - 苯并吡喃 - 6 - 醇，二盐酸盐）对抗原诱导的晚期（16小时）气道高反应性、炎症细胞数量增加、水肿以及支气管肺泡灌洗（BAL）液中炎症介质释放的影响。抗原激发后，观察到气管和上支气管对乙酰胆碱和组胺的体外反应性增加，以及BAL液中白细胞数量增加，主要是嗜酸性粒细胞和单核细胞。抗原激发后，BAL液中蛋白质、组胺和PGE2的浓度也分别显著增加了53%、57%和216%。在抗原激发前17小时和3小时以及激发后6小时腹腔注射U - 83836E（10 mg/kg），可使气道中的总细胞数和BAL液蛋白含量降低约80%。此外，这种治疗完全抑制了气道高反应性。U - 83836E治疗对BAL液中的组胺和PGE2水平没有显著影响。这些结果表明，U - 83836E对卵清蛋白致敏豚鼠哮喘的一些特征有效。
