【摘要】 目的 探讨血小板活化因子(PAF)在猪急性重症胰腺炎(ASP)性肺和气管粘膜损伤中的作用机制，观察一种新型PAF受体拮抗剂(BN50739)对ASP后肺和气管粘膜中嗜中性粒细胞(PMN)弹性蛋白酶(NE)和磷脂酶A2(PLA2)活性的影响。方法 选健康长白种猪28只，体重16～22 kg，雌雄不限，随机分为5组：Ⅰ组(假手术对照组，5只)；Ⅱ组(ASP对照组(6只)；Ⅲ组［二甲亚砜(DMSO)对照组，5只)；Ⅳ组(ASP+PAF受体拮抗剂预防组，6只)，在ASP诱导前30 min静脉注射BN50739 10 mg/kg；Ⅴ组(ASP+PAS受体拮抗剂治疗组，6只)，在ASP诱导后6 h静脉注射BN50739 10 mg/kg，此后按5 mg/kg，q 8 h。在麻醉状态下，进腹向胰总管内注入1 ml/kg 5%牛磺胆酸钠混合液诱导ASP。以0.9% NaCl磷酸盐缓冲液取代5%牛磺胆酸钠混合液即为假手术对照组。观察72 h后用10% KCl处死，立即留取若干重肺和气管粘膜组织置于液氮中保存，以检测组织中PAF、NE、PLA2和髓过氧化物酶(MPO)的变化。结果 ASP导致肺和气管粘膜组织中PAF、NE、PLA2及肺组织中MPO含量明显升高，且组织中NE、PLA2及MPO活性与PAF水平呈非常显著正相关(P分别＜0.01、0.01、0.05)。预防或治疗性给予BN50739可不同程度地减轻ASP后氧自由基介导性肺和气管粘膜损伤。以前者效果更为确切。结论 PAF在ASP后急性肺损伤中起着重要作用，可能与PAS引起肺PMN扣押、NE和PLA2水平升高密切相关。预防或治疗性应用BN50739可明显减少ASP肺PMN扣押、降低NE和PLA2水平，从而保护ASP后肺损伤。Influences of BN50739 on neutrophil elastase and phospholipase A2 in lung and tracheal mucosa of pigs with acute severe pancreatitis
TU Weifeng, LI Jieshou, ZHU Weiming, et al.
(Institute of General Research, Nanjing General Hospital, Nanjing 210002, China)
【Abstract】 Objective To investigate the effects of platelet-activating factor (PAF) and a new potent PAF-receptor antagonist, BN50739, on the activities of neutrophil elastase and phospholipase A2 (PLA2) in lung and tracheal mucosa of pigs with acute severe pancreatitis (ASP) induced by sodium taurocholate.Methods There were twenty eight pigs weighing 16～22 kg, which were divided into five groups. Group Ⅰ (n=5):sham-control; Group Ⅱ (n=6): ASP-control; Group Ⅲ (n=5): DMSO-control; Group Ⅳ (n=6) and Group Ⅴ (n=6): pre-and post-treatment with BN50739. Anesthesized pigs were subjected to ASP induced by injecting 1 ml/kg of combined solution of 5% sodium taurocholate and 8 000～10 000 BAEE units trypsin/ml into pancreas via pancreatic duct. All pigs were sacrificed by injecting 20 ml of 10% KCl intravenously. Specimens of lung and tracheal mucosa were removed, weighed and homogenize
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