Spencer D A, Evans J M, Green S E, Piper P J, Costello J F
Department of Thoracic Medicine King's College School of Medicine and Dentistry, London.
Thorax. 1991 Jun;46(6):441-5. doi: 10.1136/thx.46.6.441.
To determine whether the effects of platelet activating factor on the airways may be due to the production of leukotrienes we studied the effects of pretreatment with the selective cysteinyl leukotriene antagonist SK&F 104353-Z2 on the airway and cellular responses to inhaled platelet activating factor. Eight healthy men were studied in a randomised, double blind placebo controlled cross-over study. A single dose of platelet activating factor that caused a fall of at least 35% in specific airways conductance (sGaw) was determined initially for each subject. Challenge with this dose of platelet activating factor was then carried out on two further occasions after pretreatment with a single nebulised dose of SK&F 104353-Z2 or placebo. The % reductions in specific airways conductance and of partial flow at 30% of vital capacity (PVmax30) were less after SK&F 104353-Z2 than after placebo (22 versus 34 for sGaw, 19 versus 31 for PVmax30). The mean (95% confidence limits (CL] differences in the maximum % fall from control values for SK&F 104353-Z2 and placebo were -12.6 (-23.8, -1.4) for sGaw and -12.5, (-20.8 -4.2) for PVmax30. The mean % fall in neutrophil count was similar after SK&F 104353-Z2 (46%) and after placebo (50%) (95% CL of difference 13.6, 6.6). Bronchial responsiveness to methacholine did not increase above baseline values in any subject when measured two weeks after challenge by platelet activating factor. This study suggests that leukotrienes play a part in the response to platelet activating factor in man.
为了确定血小板活化因子对气道的作用是否可能归因于白三烯的产生，我们研究了用选择性半胱氨酰白三烯拮抗剂SK&F 104353-Z2预处理对气道和细胞对吸入血小板活化因子反应的影响。在一项随机、双盲、安慰剂对照的交叉研究中对8名健康男性进行了研究。最初为每个受试者确定了单剂量的血小板活化因子，该剂量导致特定气道传导率（sGaw）至少下降35%。在用单剂量雾化的SK&F 104353-Z2或安慰剂预处理后，再进行两次该剂量血小板活化因子的激发试验。与安慰剂相比，SK&F 104353-Z2处理后特定气道传导率和肺活量30%时的部分流速（PVmax30）的降低百分比更小（sGaw分别为22%和34%，PVmax30分别为19%和31%）。SK&F 104353-Z2和安慰剂与对照值相比最大降低百分比的均值（95%置信区间[CL]）差异，sGaw为-12.6（-23.8，-1.4），PVmax30为-12.5（-20.8，-4.2）。SK&F 104353-Z2处理后中性粒细胞计数的平均降低百分比（46%）与安慰剂处理后（50%）相似（差异的95%CL为13.6，6.6）。在用血小板活化因子激发试验两周后测量时，任何受试者对乙酰甲胆碱的支气管反应性均未高于基线值。这项研究表明白三烯在人类对血小板活化因子的反应中起作用。
