title: Protective effects of MCP-1 inhibitor on a rat model of severe acute pancreatitis.
abstract: 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 biliopancreatic 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 bilipancreatic 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China. zhouguoxiong@medmail.com.cn
authors.forename: Guo-Xiong
authors.initials: GX
authors.lastname: Zhou
authors.forename: Xue-Juan
authors.initials: XJ
authors.lastname: Zhu
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Ding
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Qiang
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D007150:Immunohistochemistry; D007191:Indazoles / Q000627:therapeutic use*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011422:Propionates / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007191:Indazoles; D011422:Propionates; D012333:RNA, Messenger; D000681:Amylases; C079489:bindarit