Ahmed T, Abraham W M, D'Brot J
Division of Pulmonary Disease, University of Miami School of Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140.
Am Rev Respir Dis. 1992 Mar;145(3):566-70. doi: 10.1164/ajrccm/145.3.566.
The glycosaminoglycan heparin has been shown to block inositol triphosphate (IP3) receptors in various tissues. Because IP3 is one of the pathways involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit airway anaphylaxis. Thus, the purpose of the present investigation was to study the effect of inhaled heparin on immunologically and nonimmunologically induced bronchoconstriction in allergic sheep. Specific lung resistance (SRL) was measured in 15 sheep allergic to Ascaris suum antigen, before and after inhalation challenge with the specific antigen, compound 48/80, histamine, and carbachol. On a different day, the animals were pretreated with inhaled heparin and airway challenges with the antigen and agonists were repeated. Antigen alone increased SRL by 367 +/- 119% (mean +/- SE) above baseline (p less than 0.05). Inhaled heparin had no effect on baseline SRL, but attenuated antigen-induced bronchoconstriction in a dose-dependent fashion: mean SRL increased by 313 +/- 87, 151 +/- 69, and 24 +/- 20% above baseline with 100, 300, and 1,000 U/kg of heparin, respectively. Inhaled benzyl alcohol preservative, dextran sulfate, and de-N-sulfated heparin failed to inhibit antigen-induced bronchoconstriction. The dose of heparin (1,000 U/kg) that completely blocked antigen-induced bronchoconstriction also attenuated the bronchoconstriction induced by compound 48/80 (delta SRL = 374 +/- 72 versus 35 +/- 12%), but failed to block the bronchoconstrictor effects of histamine and carbachol. These data suggest that inhaled heparin prevents bronchoconstrictor responses induced by by stimuli that produce immunologic and nonimmunologic mast-cell degranulation in sheep, without attenuating agonist-induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
已证实糖胺聚糖肝素可阻断多种组织中的肌醇三磷酸（IP3）受体。由于IP3是参与肥大细胞刺激 - 分泌偶联的途径之一，肝素可能抑制气道过敏反应。因此，本研究的目的是研究吸入肝素对变应性绵羊免疫性和非免疫性诱导的支气管收缩的影响。在15只对猪蛔虫抗原过敏的绵羊中，测量了特异性肺阻力（SRL），分别在吸入特异性抗原、化合物48/80、组胺和卡巴胆碱激发前后进行测量。在不同的一天，动物先用吸入肝素预处理，然后重复抗原和激动剂引起的气道激发。单独抗原使SRL比基线增加367±119%（平均值±标准误）（p<0.05）。吸入肝素对基线SRL无影响，但以剂量依赖方式减弱抗原诱导的支气管收缩：使用100、300和1000 U/kg肝素时，平均SRL分别比基线增加313±87%、151±69%和24±20%。吸入苯甲醇防腐剂、硫酸葡聚糖和去N - 硫酸化肝素未能抑制抗原诱导的支气管收缩。完全阻断抗原诱导支气管收缩的肝素剂量（1000 U/kg）也减弱了化合物48/80诱导的支气管收缩（SRL变化 = 374±72%对35±12%），但未能阻断组胺和卡巴胆碱的支气管收缩作用。这些数据表明，吸入肝素可预防绵羊中由产生免疫性和非免疫性肥大细胞脱颗粒的刺激所诱导的支气管收缩反应，而不减弱激动剂诱导的支气管收缩。（摘要截断于250字）
