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 (BN5 0 739)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 2 8只 ,体重 16～ 2 2kg ,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 30min静脉注射BN5 0 73910mg/kg ;Ⅴ组 (ASP +PAS受体拮抗剂治疗组 ,6只 ) ,在ASP诱导后 6h静脉注射BN5 0 73910mg/kg,此后按 5mg/kg ,q 8h。在麻醉状态下 ,进腹向胰总管内注入 1ml/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 72h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 0 1、0 0 1、0 0 5 )。预防或治疗性给予BN5 0 739可不同程度地减轻ASP后氧自由基介导性?
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 A 2 (PLA 2) 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 homogenized in grinding tubes. The homogenate was centrifuged and the supernatants were collected for the assays of NE, PLA 2, MPO and PAF. Results The activities of NE, PLA 2 and MPO and the levels of PAF in lung and tracheal mucosa increased significantly in ASP pigs. There are significantly positive relationships between PAF and NE, PLA 2, MPO or W/D in lung and tracheal mucosa. The PAF levels in lung and tracheal mucosa and the severity of acute lung injury induced by PMN sequestration, NE and activated PLA 2 reduced remarkably by the pre and post treatment with BN50739. Conclusions PAF plays an important role in acute lung injury in porcine ASP, which may be associated with the increments of PMN sequestration, NE and the highly activated PLA 2 in lung and tracheal mucosa. The pre and post treatment with BN50739 can effectively reduce the PAF levels in lung and tracheal mucosa and the severity of acute lung injury following ASP via reducing the PMN sequestration and the amount of elastase, and by inhibiting PLA 2 activities in lung and tracheal mucosa.
出处
《中华结核和呼吸杂志》
CSCD
北大核心
2000年第10期595-598,共4页
Chinese Journal of Tuberculosis and Respiratory Diseases
