Lin C C, Lin C Y
Chest Division, Mackay Memorial Hospital, Taipei, Taiwan.
J Asthma. 1997;34(2):153-60. doi: 10.3109/02770909709075660.
Using a forced expiratory maneuver to measure flow volume loops, we evaluated the ability of platelet activating factor (PAF) to induce acute bronchospasm and in histological changes associated with bronchial asthma in guinea pigs. We determined both the dose-response curve and the time course of PAF-induced bronchoconstriction. Eight guinea pigs with weights ranging from 350 to 450 g were anesthetized, tracheotomized, and then paralyzed with gallamine. Baseline pulmonary function tests (PFT) were done. Different doses (25, 50, 100, 200, and 500 ng/kg) of PAF were injected through the jugular vein, and serial PFTs were done at 30 sec, 2, 5, and 20 min after each dose of PAF. Acetylcholine provocation testing was done following the 200 ng/kg dose of PAF. The PFTs included a forced expiratory maneuver, airway opening pressure (PaO), and total lung compliance (TLC). After all PFTs were completed, cell counts were done on fluid obtained from bronchoalveolar lavage (BAL) and the lungs were removed for histological study. Eight other guinea pigs were used as controls. The results showed that with increasing doses of PAF from 25 ng/kg to 200 ng/kg, all lung function parameters, including vital capacity, peak flow, MFEF 75%, MFEF 50%, MFEF 25%, and total lung compliance, gradually decreased. However, a further increase of the dose of PAF up to 500 ng/kg did not result in continued worsening of PFTs. The most severe bronchoconstriction occurred 30 sec after PAF was injected, and it gradually resolved thereafter. PAF injection also induced a severe inflammatory reaction of the airway and lung tissue, characterized by congestion, edema, inflammatory cell (especially lymphocytes and eosinophils) infiltration, and desquamation of bronchial epithelial cells. In conclusion, in the guinea pig model, PAF can induce acute reversible bronchospasm and bronchial hyperreactivity, as well as the typical histological changes of bronchial asthma.
我们使用用力呼气动作来测量流量容积环，评估了血小板活化因子（PAF）诱导豚鼠急性支气管痉挛以及与支气管哮喘相关的组织学变化的能力。我们确定了PAF诱导支气管收缩的剂量反应曲线和时间进程。选取8只体重在350至450克之间的豚鼠，进行麻醉、气管切开，然后用加拉明使其麻痹。进行了基线肺功能测试（PFT）。通过颈静脉注射不同剂量（25、50、100、200和500纳克/千克）的PAF，在每次注射PAF后的30秒、2分钟、5分钟和20分钟进行系列PFT。在注射200纳克/千克剂量的PAF后进行乙酰胆碱激发试验。PFT包括用力呼气动作、气道开口压力（PaO）和总肺顺应性（TLC）。在所有PFT完成后，对支气管肺泡灌洗（BAL）获得的液体进行细胞计数，并取出肺组织进行组织学研究。另外8只豚鼠用作对照。结果显示，随着PAF剂量从25纳克/千克增加到200纳克/千克，所有肺功能参数，包括肺活量、峰值流量、75%最大呼气流量、50%最大呼气流量、25%最大呼气流量和总肺顺应性，逐渐下降。然而，将PAF剂量进一步增加至500纳克/千克并未导致PFT持续恶化。最严重的支气管收缩发生在注射PAF后30秒，此后逐渐缓解。注射PAF还诱导了气道和肺组织的严重炎症反应，其特征为充血、水肿、炎症细胞（尤其是淋巴细胞和嗜酸性粒细胞）浸润以及支气管上皮细胞脱落。总之，在豚鼠模型中，PAF可诱导急性可逆性支气管痉挛和支气管高反应性，以及支气管哮喘的典型组织学变化。
