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白三烯拮抗剂-抑制剂与主动致敏豚鼠对吸入抗原的支气管反应

Leukotrienes antagonist-inhibitor and the bronchial response to inhaled antigen in actively sensitized guinea-pigs.

作者信息

Marcelle R

机构信息

Institut Léon Frédéricq, Physiologie, Université de Liège, Belgium.

出版信息

Arch Physiol Biochem. 1998 Aug;105(4):358-64.

PMID:9711356
Abstract

The aim of the study was to estimate an eventual contribution of leukotrienes in respiratory mechanic changes observed in guinea-pig during bronchial anaphylaxis. Twenty-eight guinea-pigs, actively sensitized to ovalbumin, were anesthetized and curarized before being challenged, during controlled ventilation, with antigen administered as an aerosol. Antigen challenge was performed before and after pretreatment with nebulized FPL55712 and BW755C, respectively used as an antagonist of leukotrienes and as a cyclo-oxygenase/lipoxygenase inhibitor. The experiments were carried out during continuous recording of tracheal pressure (Ptr), airflow (V) and tidal volume (VT) signals variations evidencing respiratory asynchronism (AS) and allowing measurements of the changes in airway resistance (AR) and dynamic compliance (Cdyn) during all the challenge. Administration of nebulized ovalbumin was stopped at the onset of AS appearance chosen as the threshold of the antigen-induced bronchoconstriction. The results showed that separate or combined pretreatment with FPL55712 and BW755C did not significantly modify the threshold of the ovalbumin-induced bronchoconstriction in guinea-pigs. Nevertheless pretreatment with nebulized FPL55712 reduced significantly the intensity and the duration of the response of these animals to inhaled leukotriene D4 (LTD4). Moreover the response of guinea-pigs to inhaled LTD4, characterized by a starting decrease in Cdyn, appeared quite different from the response to the antigen starting by an abrupt rise in RA induced by a sudden bronchoconstriction. From these results, we concluded that leukotrienes seem not to be the main mediator of the bronchial anaphylaxis in guinea-pigs.

摘要

本研究的目的是评估白三烯在豚鼠支气管过敏反应期间观察到的呼吸力学变化中的最终作用。28只对卵清蛋白主动致敏的豚鼠在麻醉和箭毒化后,在控制通气期间接受雾化抗原激发。分别用雾化的FPL55712(用作白三烯拮抗剂)和BW755C(用作环氧化酶/脂氧化酶抑制剂)进行预处理前后进行抗原激发。实验在连续记录气管压力(Ptr)、气流(V)和潮气量(VT)信号变化的过程中进行,这些变化表明呼吸不同步(AS),并允许在所有激发过程中测量气道阻力(AR)和动态顺应性(Cdyn)的变化。在选定为抗原诱导支气管收缩阈值的AS出现时停止雾化卵清蛋白的给药。结果表明,用FPL55712和BW755C单独或联合预处理均未显著改变豚鼠卵清蛋白诱导支气管收缩的阈值。然而,用雾化的FPL55712预处理显著降低了这些动物对吸入白三烯D4(LTD4)反应的强度和持续时间。此外,豚鼠对吸入LTD4的反应,其特征是Cdyn开始下降,与对抗原的反应明显不同,抗原反应开始时是由于突然的支气管收缩导致RA突然升高。从这些结果中,我们得出结论,白三烯似乎不是豚鼠支气管过敏反应的主要介质。

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