Evans T W, Rogers D F, Aursudkij B, Chung K F, Barnes P J
Department of Clinical Pharmacology, Brompton Hospital, London, United Kingdom.
Am Rev Respir Dis. 1988 Aug;138(2):395-9. doi: 10.1164/ajrccm/138.2.395.
Antigen challenge of ovalbumin (OA)-sensitized guinea pigs results in significant (p less than 0.05) increases in vascular permeability to Evans blue (EB) dye in the airways, esophagus, and bladder. Mean values +/- SEM in ng EB/mg wet weight tissue for unsensitized versus sensitized animals were: trachea, 23.6 +/- 6.6 versus 92.5 +/- 11.1; main bronchi, 31.1 +/- 12.2 versus 153.1 +/- 14.9; "central" intrapulmonary airways (ipa), 34.6 +/- 11.2 versus 101.3 +/- 6.2; and "peripheral" ipa, 26.2 +/- 6.8 versus 93.5 +/- 13.6. We investigated the involvement of several mediators of inflammation in this process. FPL 55712, a sulfidopeptide leukotriene receptor antagonist, caused significant inhibition of leakage in trachea (to 55.1 +/- 9.8) and main bronchi (91.7 +/- 15.8). Blockade of the cyclooxygenase and lipoxygenase pathways with BW 755C, but not of the cyclooxygenase pathway alone with indomethacin, also significantly reduced EB dye extravasation in trachea (55.1 +/- 18.0), main bronchi (71.7 +/- 23.0), and "central" ipa (62.7 +/- 16.4). The histamine antagonists, chlorpheniramine and cimetidine, only inhibited microvascular leakage in main bronchi (94.4 +/- 20.0). PAF-receptor blockade with the ginkgolide mixture BN 52063 had no effect. Nedocromil sodium, a mast cell stabilizer and an inhibitor of inflammatory cell activation, caused significant inhibition throughout the airways: trachea, 50.4 +/- 10.6; main bronchi, 72.0 +/- 15.3; "central" ipa 61.0 +/- 8.6; "peripheral" ipa 41.9 +/- 12.2. Thus, histamine and lipoxygenase products (in particular, leukotrienes), but not PAF, may mediate the antigen-induced increase in vascular permeability to different degrees in differing regions of the respiratory tract in guinea pigs.
用卵清蛋白（OA）致敏豚鼠后进行抗原激发，可导致气道、食管和膀胱对伊文思蓝（EB）染料的血管通透性显著增加（p<0.05）。未致敏与致敏动物每毫克湿重组织中EB的平均含量（ng）±标准误分别为：气管，23.6±6.6与92.5±11.1；主支气管，31.1±12.2与153.1±14.9；肺内“中央”气道（ipa），34.6±11.2与101.3±6.2；以及肺内“外周”气道，26.2±6.8与93.5±13.6。我们研究了几种炎症介质在这一过程中的作用。硫化肽白三烯受体拮抗剂FPL 55712可显著抑制气管（降至55.1±9.8）和主支气管（91.7±15.8）的渗漏。用BW 755C阻断环氧化酶和脂氧合酶途径，但单独用吲哚美辛阻断环氧化酶途径，也可显著减少气管（55.1±18.0）、主支气管（71.7±23.0）和肺内“中央”气道（62.7±16.4）中EB染料的渗出。组胺拮抗剂氯苯那敏和西咪替丁仅抑制主支气管的微血管渗漏（94.4±20.0）。用银杏内酯混合物BN 52063阻断PAF受体无效。色甘酸钠是一种肥大细胞稳定剂和炎症细胞活化抑制剂，可在整个气道中产生显著抑制作用：气管，50.4±10.6；主支气管，72.0±15.3；肺内“中央”气道61.0±8.6；肺内“外周”气道41.9±12.2。因此，组胺和脂氧合酶产物（特别是白三烯）而非PAF，可能在不同程度上介导了豚鼠呼吸道不同区域抗原诱导的血管通透性增加。
