血小板活化因子拮抗剂对猪急性重症胰腺炎后肺和气？…

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）和磷麦Ａ２（ＰＬＡ２）活性的影响。方法 选健康长白种猪２８只，体重１６￣２２ｋｇ，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「二甲亚砚（ＤＭＳＯ）对照组，

Influences of BN50739 on neutrophil elastase and phospholipase A_2 in lung and tracheal mucosa of pigs with acute severe pancreatitis

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 homogenized in grinding tubes. The homogenate was centrifuged and the supernatants were collected for the assays of NE, PLA2, MPO and PAF. RESULTS: The activities of NE, PLA2 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, PLA2, 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 PLA2 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 PLA2 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 PLA2 activities in lung and tracheal mucosa.