Effect Of The Proteasome Inhibitor MG132 On Acute Pancreatitis And Acute Pancreatitis-associated Lung Injury In Mice

Objective To investigate the protective effects and the potential mechanisms of proteasome inhibitor MG132 on acute pancreatitis(AP)and acute pancreatitis-associated lung injury in mice.Methods Forty-five BalB/c mice were randomly allocated to nine groups:control 3h,6h,12h group(n=5);AP 3h,6h,12h group(n=5) and MG132 3h,6h,12h group(n=5).AP group were induced by injection intraperitoneally(ip) 100μg/kg cerulein sixtimes with an interval of 1h.Control group received physiological saline(PS) in the same manner.MG132 group were injected intraperitoneally(ip) 10mg/kg MG132,30 minutes before induction AP.The levels of serum amylase(SMY)and soluble intercellular adhesion molecule–1(sICAM-1)were tested,the pathological changes of pancreas and lungs were observed,the expression of proteins of NF-кB were examined by immunohistochemistry, the expression of ICAM-1 mRNA was analyzed by reverse transcription-polymerase chain reaction(RT-PCR),the expression of proteins of chmokine monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were examined by immune- ohistochemistry.Results Compared with control group,the levels of serum amylase and soluble intercellular adhesion molecule–1(sICAM-1) significantly increased in AP group,the scores of pathological changes increased in the pancreas and lungs (P<0.05 or P<0.01),the expression of NF-кB,ICAM-1 mRNA,MCP-1and MIP-2 were over-expressed(P<0.05 or P<0.01).In MG132 group the levels of serum amylase and the soluble intercellular adhesion molecule–1(sICAM-1) markedly decreased,the scores of pathological changes decreased in the pancreas and lungs(P<0.05 or P<0.01),the expression of NF-кB,ICAM-1 mRNA,MCP-1and MIP-2 lowered than those in AP group(P<0.05 or P<0.01).Conclusions The proteasome inhibitor MG132 could obviously improved the acute pancreatitis and pancreatitis-associated lung injury,the mechanism might be related to downregulate the expression of adhesion molecule and chemotatic factor through the inhibition of NF-кB activity.