Song P, Crimi E, Milanese M, Duan J, Rehder K, Brusasco V
Centro di Fisiopatologia Respiratoria, Dipartimento di Scienze Motorie e Riabilitative, Università di Genova, Genova, Italy.
Am J Respir Crit Care Med. 1998 Dec;158(6):1809-14. doi: 10.1164/ajrccm.158.6.9801105.
Antigen challenge causes beta2-adrenoceptor dysfunction in sensitized human bronchi (Am. J. Respir. Crit. Care Med. 1997;155:1230-1234). This study investigated whether the dysfunction can be prevented by anti-inflammatory agents. Human bronchial rings (2 to 4 mm) from surgery were passively sensitized to house dust mite and challenged (1) with allergen only, (2) with allergen plus indomethacin (10(-)5 M), (3) with allergen plus nedocromil sodium (10(-)7 M to 10(-)5 M), (4) with allergen plus the H1-receptor antagonist cetirizine (10(-)7 M to 10(-)5 M), and (5) with allergen plus the peptido-leukotriene receptor antagonist iralukast (10(-)7 M to 10(-)5 M). Rings were first contracted with 10(-)6 M carbachol and then relaxed with salbutamol (10(-)9 M to 10(-)4 M). The concentration-relaxation curve to salbutamol was shifted significantly to the right in the rings challenged with allergen only compared with control rings. In the rings challenged with allergen plus nedocromil sodium (10(-)6 M and 10(-)5 M) or iralukast (10(-)6 M and 10(-)5 M) the concentration-relaxation curves to salbutamol were significantly shifted to the left compared with rings challenged in saline alone, suggesting a protective effect against beta2-adrenoceptor dysfunction. Neither allergen plus cetirizine nor allergen plus indomethacin shifted significantly the concentration-relaxation curves to salbutamol compared with rings challenged in saline alone. We conclude that the release of peptido-leukotrienes may play a significant role in causing the allergen-induced beta2-receptor dysfunction in passively sensitized human bronchi.
抗原激发可导致致敏人支气管中的β2 - 肾上腺素能受体功能障碍（《美国呼吸与危重症医学杂志》1997年；155:1230 - 1234）。本研究调查了抗炎药物是否能预防这种功能障碍。取自手术的人支气管环（2至4毫米）被被动致敏于屋尘螨并接受激发：（1）仅用变应原激发，（2）用变应原加吲哚美辛（10⁻⁵ M）激发，（3）用变应原加奈多罗米钠（10⁻⁷ M至10⁻⁵ M）激发，（4）用变应原加H1受体拮抗剂西替利嗪（10⁻⁷ M至10⁻⁵ M）激发，以及（5）用变应原加肽白三烯受体拮抗剂依拉鲁司特（10⁻⁷ M至10⁻⁵ M）激发。支气管环先用10⁻⁶ M卡巴胆碱收缩，然后用沙丁胺醇（10⁻⁹ M至10⁻⁴ M）舒张。与对照环相比，仅用变应原激发的支气管环中，沙丁胺醇的浓度 - 舒张曲线显著右移。与仅在盐水中激发的支气管环相比，用变应原加奈多罗米钠（10⁻⁶ M和10⁻⁵ M）或依拉鲁司特（10⁻⁶ M和10⁻⁵ M）激发的支气管环中，沙丁胺醇的浓度 - 舒张曲线显著左移，提示对β2 - 肾上腺素能受体功能障碍有保护作用。与仅在盐水中激发的支气管环相比，变应原加西替利嗪或变应原加吲哚美辛均未使沙丁胺醇的浓度 - 舒张曲线发生显著移位。我们得出结论，肽白三烯的释放可能在被动致敏的人支气管中导致变应原诱导的β2受体功能障碍方面起重要作用。
