BACKGROUND:Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis.This study aimed to establish a rat model of severe acute pancreatitis(SAP) for investigating monocyte chemotactic pro...BACKGROUND:Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis.This study aimed to establish a rat model of severe acute pancreatitis(SAP) for investigating monocyte chemotactic protein-1(MCP-1) expression in the pathogenesis of the disease.We assessed the effects of the inhibitor of MCP-1,Bindarit,on SAP and explored the mechanisms underlying SAP. METHODS:Seventy-two Sprague-Dawley rats were randomly divided into a saline control group(group S),an SAP group (group P),and a Bindarit group(group T).The SAP model was induced by retrograde infusion of 4%sodium taurocholate into the bilio-pancreatic duct.Based on the SAP model,Bindarit was injected intraperitoneally in group T,and 0.5% methyl cellulose was injected intraperitoneally in groups S and P.In group S,saline was retrogradely infused into the bili- pancreatic duct.Serum amylase levels and the histological changes in the pancreas were assessed at different time- points in each group.Expression of MCP-1 in serum was measured by enzyme-linked immunoadsorbent assay(ELISA). MCP-1 protein and mRNA expression levels were detected by immunohistochemistry,Western blotting,and semi- quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS:Serum amylase levels in groups P and T were higher than those in group S.Serum amylase levels were significantly lower in group T than in group P at 6 and 12 hours after operation.The levels of MCP-1 in serum at 6 and 12 hours after operation in group P were significantly higher than in group S,and significantly lower in group T than in group P at 6 and 12 hours after operation.The pathological damage in the pancreas was milder in group T than in group P.MCP-1 protein and mRNA expression levels in the pancreas were higher in groups P and T than in group S.These expression levels were positively correlated with the pathological damage of pancreatic tissues.The activity of MCP-1 in group T was significantly lower than in group P.CONCLUSION:MCP-1 may play important roles in the pathogenesis of SAP.The data suggest that Bindarit ameliorates SAP by inhibiting the activity of MCP-1 in vivo.展开更多
基金supported by grants from the social Burteall Foundation of Nantong(S5054)
文摘BACKGROUND:Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis.This study aimed to establish a rat model of severe acute pancreatitis(SAP) for investigating monocyte chemotactic protein-1(MCP-1) expression in the pathogenesis of the disease.We assessed the effects of the inhibitor of MCP-1,Bindarit,on SAP and explored the mechanisms underlying SAP. METHODS:Seventy-two Sprague-Dawley rats were randomly divided into a saline control group(group S),an SAP group (group P),and a Bindarit group(group T).The SAP model was induced by retrograde infusion of 4%sodium taurocholate into the bilio-pancreatic duct.Based on the SAP model,Bindarit was injected intraperitoneally in group T,and 0.5% methyl cellulose was injected intraperitoneally in groups S and P.In group S,saline was retrogradely infused into the bili- pancreatic duct.Serum amylase levels and the histological changes in the pancreas were assessed at different time- points in each group.Expression of MCP-1 in serum was measured by enzyme-linked immunoadsorbent assay(ELISA). MCP-1 protein and mRNA expression levels were detected by immunohistochemistry,Western blotting,and semi- quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS:Serum amylase levels in groups P and T were higher than those in group S.Serum amylase levels were significantly lower in group T than in group P at 6 and 12 hours after operation.The levels of MCP-1 in serum at 6 and 12 hours after operation in group P were significantly higher than in group S,and significantly lower in group T than in group P at 6 and 12 hours after operation.The pathological damage in the pancreas was milder in group T than in group P.MCP-1 protein and mRNA expression levels in the pancreas were higher in groups P and T than in group S.These expression levels were positively correlated with the pathological damage of pancreatic tissues.The activity of MCP-1 in group T was significantly lower than in group P.CONCLUSION:MCP-1 may play important roles in the pathogenesis of SAP.The data suggest that Bindarit ameliorates SAP by inhibiting the activity of MCP-1 in vivo.
