Martinez-Salas J, Mendelssohn R, Abraham W M, Hsiao B, Ahmed T
Division of Pulmonary Diseases, University of Miami School of Medicine, Mount Sinai Medical Center, Florida 33140, USA.
J Appl Physiol (1985). 1998 Jan;84(1):222-8. doi: 10.1152/jappl.1998.84.1.222.
Inhaled heparin prevents antigen-induced bronchoconstriction and inhibits anti-immunoglobulin E-mediated mast cell degranulation. We hypothesized that the antiallergic action of heparin may be molecular weight dependent. Therefore, we studied the effects of three different low-molecular-weight fractions of heparin [medium-, low-, and ultralow-molecular-weight heparin (MMWH, LMWH, ULMWH, respectively)] on the antigen-induced acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 22 sheep before and after airway challenge with Ascaris suum antigen, without and after pretreatment with inhaled fractionated heparins at doses of 0.31-5.0 mg/kg. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units that increased specific lung resistance by 400%. All fractionated heparins caused a dose-dependent inhibition of ABR and AHR. ULMWH was the most effective fraction, with the inhibitory dose causing 50% protection (ID50) against ABR of 0.5 mg/kg, whereas ID50 values of LMWH and MMWH were 1.25 and 1.8 mg/kg, respectively. ULMWH was also the most effective fraction in attenuating AHR; the ID50 values for ULMWH, LMWH, and MMWH were 0.5, 2.5, and 4.7 mg/kg, respectively. These data suggest that 1) fractionated low-molecular-weight heparins attenuate antigen-induced ABR and AHR; 2) there is an inverse relationship between the antiallergic activity of heparin fractions and molecular weight; and 3) ULMWH is the most effective fraction preventing allergic bronchoconstriction and airway hyperresponsiveness.
吸入性肝素可预防抗原诱导的支气管收缩，并抑制抗免疫球蛋白E介导的肥大细胞脱颗粒。我们推测肝素的抗过敏作用可能与分子量有关。因此，我们研究了三种不同低分子量肝素组分[分别为中分子量、低分子量和超低分子量肝素（MMWH、LMWH、ULMWH）]对变应性绵羊抗原诱导的急性支气管收缩反应（ABR）和气道高反应性（AHR）的影响。在22只绵羊用猪蛔虫抗原进行气道激发前后，以及在吸入剂量为0.31 - 5.0 mg/kg的分级肝素预处理前后，测量其特异性肺阻力。在抗原激发前和激发后2小时评估气道反应性，以增加特异性肺阻力400%的呼吸单位中卡巴胆碱的累积激发剂量来衡量。所有分级肝素均引起ABR和AHR的剂量依赖性抑制。ULMWH是最有效的组分，其抑制剂量导致对ABR的50%保护（ID50）为0.5 mg/kg，而LMWH和MMWH的ID50值分别为1.25和1.8 mg/kg。ULMWH在减轻AHR方面也是最有效的组分；ULMWH、LMWH和MMWH的ID50值分别为0.5、2.5和4.7 mg/kg。这些数据表明：1）分级低分子量肝素可减轻抗原诱导的ABR和AHR；2）肝素组分的抗过敏活性与分子量呈负相关；3）ULMWH是预防过敏性支气管收缩和气道高反应性最有效的组分。
