Evans T W, McAnulty R J, Rogers D F, Chung K F, Barnes P J, Laurent G J
Department of Thoracic Medicine, Brompton Hospital, London, UK.
Environ Health Perspect. 1990 Apr;85:65-9. doi: 10.1289/ehp.85-1568314.
Bleomycin is a highly effective antitumor agent, but pulmonary toxicity, characterized by an acute inflammatory reaction and associated pulmonary edema, limits clinical use of the drug. Platelets and platelet-activating factor (PAF), a membrane-derived phospholipid, have been implicated in the mechanisms that can mediate pulmonary microvascular injury. We sought to investigate the role of PAF in bleomycin-induced lung injury in the rat, using the PAF receptor antagonist BN 52021; and the role of platelets though the use of an anti-platelet antibody. Lung injury was induced by intratracheal bleomycin (1.5 mg) and assessed by measurements of lung wet weight and total pulmonary extravascular albumin space (TPEAS). Bleomycin caused a significant increase in both indices after 48 hr, compared with control animals (p less than 0.05). A single dose of BN 52021 (20 mg/kg orally) significantly reduced the bleomycin-induced increase in lung weight, but not the rise in TPEAS (p greater than 0.05). Increasing the dose of BN 52021 (20 mg/kg/12 hr, orally) had no additional effect. Reducing circulating platelet numbers by approximately 75% had no effect on either the increase in lung weight or TPEAS, observed 48 hr after bleomycin (p greater than 0.05). PAF may partially contribute to the acute inflammatory reaction seen after intratracheal bleomycin in rats.
博来霉素是一种高效抗肿瘤药物，但以急性炎症反应及相关肺水肿为特征的肺毒性限制了该药物的临床应用。血小板和血小板活化因子（PAF，一种膜衍生磷脂）参与了介导肺微血管损伤的机制。我们试图使用PAF受体拮抗剂BN 52021来研究PAF在博来霉素诱导的大鼠肺损伤中的作用；并通过使用抗血小板抗体来研究血小板的作用。通过气管内注射博来霉素（1.5毫克）诱导肺损伤，并通过测量肺湿重和总肺血管外白蛋白间隙（TPEAS）进行评估。与对照动物相比，博来霉素在48小时后使这两个指标均显著增加（p小于0.05）。单次口服BN 52021（20毫克/千克）可显著降低博来霉素诱导的肺重量增加，但对TPEAS的升高无影响（p大于0.05）。增加BN 52021的剂量（20毫克/千克/12小时，口服）没有额外效果。将循环血小板数量减少约75%对博来霉素注射48小时后观察到的肺重量增加或TPEAS均无影响（p大于0.05）。PAF可能部分导致大鼠气管内注射博来霉素后出现的急性炎症反应。
