N-acetylcysteine decreases the severity of pancreatic injury in rats with acute necrotizing pancreatitis / 中华普通外科杂志

ABSTRACT

Objective To investigate the correlation between pancreatic nuclear factor-κB (NF-κB) activation, cell apoptosis and pancreatic injury. To determine effects of N-acetylcysteine (NAC) on pancreatic injury in rats with acute necrotizing pancreatitis (ANP). Methods Thirty-three Wistar rats were divided into five groups: normal group, normal saline (NS) group, ANP group, prophylactic and therapeutic groups with NAC randomly. ANP was produced by 3.5% sodium taurocholate retrograde injection. In the prophylactic group, rats received intravenous (i. v.) injection of NAC (300 mg/kg) 1 hour before taurocholate injection and in the therapeutic group, NAC i.v. injection was given 1 hour after sodium taurocholate injection. Animals were sacrificed at 12 hours after induction of pancreatitis. Activation of NF-KB in pancreatic tissues was determined by electrophoretic mobility shift assay(EMSA). Cell apoptosis was assessed by modified TUNEL method. The following parameters were also measured: plasma levels of amylase and lipase, pancreatic wet/dry weight ratio and histologic grading. Results Taurocholate pancreatitis is characteristic of necrosis, haemorrhage, and severe leukocyte infiltration in the pancreas. Plasma amylase and lipase levels, pancreatic wet/dry weight ratio increased in rats of ANP. NF-κB banding activity was higher after pancreatitis induction (6.03±0.41). When NAC was given 1 hour before induction of pancreatitis, the activation (3.28±0.42) of NF-κB was prevented with significantly decreased severity of pancreatitis as assessed by amylase, pancreatic wet/dry weight ratio. The number of apoptotic cells in pancreatic tissue sections was greater in rats treated with NAC than in rats not treated with NAC. There was a negative correlation between NF-κB banding activity and apoptosis of pancreatic cells (r=-0.96, P< 0.01) and there was a positive correlation between NF-κB activation and histopathological score (r=0.63, P<0.01). Histopathological score of pancreatic injury had negative correlation with apoptosis of pancreatic cells(r=-0.98, P<0.01). Conclusion Early blocked NF-κB activation with NAC increases cell apoptosis in pancreatic tissue and decreases edema of pancreas and severity of pancreatitis in rats with ANP.