The Role Of Nuclear Factor -κB And Its Inhibitor In Acute Necrotizing Pancreatitis

Objective:To investigate the activity of nuclear factor-κB (NF-κB) in pancrea tissue and serum IL-1βof rats with L-Arginine-induced acute necrotizing pancreatitis,and to assess the effectiveness of N-Acetylcysteine, an inhibitor of NF-κB,on the activity of NF-κB and on the pathological severity.Methods:SD male rats were divided into control group (C group),acute pancreatitis group (A group) and NAC intervention group (N group).In A and N groups,rats were injected twice intraperitoneally with 8% L-Arginine (2×1.2mg/g) in an interval of 1 hour to induce acute necrotizing pancreatitis.N group received a dose of NAC (0.05mg/g) intraperitoneally pretreatment additionally 1 hour before the start of the L-Arginine-induced.And the C group was administered with Saline alternatively.Rats were killed at 6th, 12th, 24th, 36th, 48th and 72th hours after the first L-Arginine injection.The subunit p65 of NF-κB in pancreas nuclear extractive, IL-1β in serum was assayed with Enzyme-linked immunoadsordent assay (ELISA), pathologic changes of pancreatic tissue were scored according to Rongione's standard.Results: The subunit p65 of NF-κB in pancreas nuclear extractive in A group significantly increased in earlier period after pancreatitis induction,whereas,it was almost completely suppressed in N group that was pretreated with NAC. IL-1β in serum in A group increased significantly in earlier period compared with N group, otherwise, it was suppressed notably in N group.The pancreata were also evaluated for their pathologic changes,sections taken from A group animalsshowed disturbance of glandular lobules and acinar cell,prevalent edema and neutrophils infiltration were also observed in A group animals,and the presence of necrosis was showed from focally to massively.The pathologic changes reached its peak at 48 hours after the first L-Arginine injection.The severity of the changes in N group were significantl slighter than that in A group.Conclusions:The activation of NF-κB at the onset of ANP was sufficient for the trigger of pancreata damage and played a indispensable injurious role in it. The high and continuing concentrations of IL-1β in serum in earlier period of ANP may play a role in regulation of NF-κB.Pretreatment with antioxidant NAC to inhibit the activation of NF-κB may reduce the degrees of damage of pancreas and be beneficial in ANP.