[Influences of BN50739 on neutrophil elastase and phospholipase A2 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.
Tu
W
W
Institute of General Research, Nanjing General Hospital, Nanjing 210002, China.
Li
J
J
Zhu
W
W
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D005260:Female; D019272:Leukocyte Elastase / Q000378:metabolism*; D008168:Lung / Q000201:enzymology*; D008297:Male; D019283:Pancreatitis, Acute Necrotizing / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011897:Random Allocation; D020545:Respiratory Mucosa / Q000201:enzymology*; D013552:Swine; D014132:Trachea / Q000201:enzymology*; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C064509:BN 50739; D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2; D019272:Leukocyte Elastase