The effects of mycophenolate mofetil on immunologic compromise in rats with severe acute pancreatitis / 中华急诊医学杂志

ABSTRACT

Objective To observe the modulatory effects of NF-κB on dynamic changes of TNF-α、IL-1β and ICAM-1 in rats with severe acute pancreatitis (SAP),and to assess the effects of pretreatment with mycophenolate mofetil (MMF) on them.Methods A total of 104 male Wistar rats were randomly divided into normal group,sham operation group,SAP group and MMF group.(1) In normal group,rats had just an incision on abdomen wall and sutured (n =8) ; (2) In sham operation group,rats underwent laparotomy with flipping over the pancreas and gendy striking five times by using blunt instrument and abdomen was closed (n =32); (3) In SAP group,SAP in rats was induced by the retrograde injection of sodium taurocholate (STC) into the pancreatic duct (n =32) ; (4) In MMF group,MMF (250mg/kg)was injected intraperitoneally one hours after injection of STC (n =32).Rats were saerificed by abdominalaorta exsanguination separately at intervals of 3,6,12 and 24 h after modeling of pancreatitis.Histologic score of pancreatic tissue was assessed,and serum amylase (AMS) and serum C-reactive protein (CRP)were measured by automatic biochemical detector.The serum levels of inflammatory cyctokines (TNF-α,1L-1β and 1CAM-1 ) were measured by using ELISA,and expression of NF-κB mRNA in pancreatic tissue was measured by using quantitative PCR.Results Compared with sham operation group,histologic score of pancreatic tissue,serum amylase,TNF-α、IL-1β and ICAM-1 in SAP group were increased significantly (P ＜ 0.05 ).Pretreatment with MMF obviously deceased histologic score,and the serum levels of amylase,TNF-α,IL-1β and ICAM-1 and the expression of NF-κB mRNA were higher than those in SAP group in early stage (P ＜0.05 ).Conclusions Cytokines play an important role in early stage of SAP.MMF could attenuate the severity of inflammatory response through inhibiting cellular immunity and modulating the proinflammatory cytokines produced.