Role of intrapulmonary expression of inducible nitric oxide synthase gene and nuclear factor-κB activation in lung injury in rats with acute necrotizing pancreatitis

Objective To explore the relationship between intrapulmonary expression of inducible nitric oxide synthase (iNOS) mRNA,nuclear factor-κ B (NF-κ B) activation and pulmonary injury in rats with acute necrotizing pancreatitis (ANP). Methods Thirty-three Wistar rats were randomized into the normal group,normal saline solution group,ANP group and prophylactic and therapeutic groups with N-acetylcysteine (NAC). ANP was inflicted with 3.5% sodium taurocholate by the method of retrograde pancreatic injection. In the prophylactic group,rats received one intravenous injection of NAC (300 mg/kg) 1 h before taurocholate injection. In the therapeutic group,a similar dose of NAC was intravenously injected 1 h after taurocholate injection. All the animals were sacrificed in 12 h after induction of pancreatitis. Activation of NF-κB in pulmonary tissues was determined with immunohistochemistry. Intrapulmonary expression of iNOS mRNA was assayed by RT-PCR. Meanwhile,plasma level of amylase,pancreatic wet/dry weight ratio and histological grading,histological grading of lung injury and intrapulmonary content of myeloperoxidase (MPO) were determined. Results NF-κB binding activity was markedly increased after induction of pancreatitis. There were intrapulmonary overexpression of iNOS mRNA and elevation of intrapulmonary content of MPO. When NAC was given 1 h before induction of pancreatitis,the activation of NF-κB was prevented and plasma level of amylase,pancreatic wet/dry weight ratio and intrapulmonary content of MPO remarkably decreased. Intrapulmonary expression of iNOS mRNA had positive correlation with activation of NF-κB and intrapulmonary content of MPO (r=0.79 and 0.66,P0.01). Conclusions The expression of iNOS mRNA and activation of NF-κB are associated with lung injury in ANP. Early blockage of NF-κB activation with NAC is effective for reducing severity of lung injury.