title: Regional arterial infusion with lipoxin A4 attenuates experimental severe acute pancreatitis.
abstract: OBJECTIVE
  Investigate the therapeutic effect of regional arterial infusion (RAI) with Aspirin-Triggered Lipoxin A4 (ATL) in experimental severe acute pancreatitis (SAP) in rats.
  
  
  METHODS
  SAP was induced by injection of 5% sodium taurocholate into the pancreatic duct. Rats with SAP were treated with ATL (the ATL group) or physiological saline (the SAP group) infused via the left gastric artery 30 min after injection of sodium taurocholate. The sham group was subjected to the same surgical procedure, though without induction of SAP. Serum levels of amylase, phospholipase A2 (PLA2), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were measured at 12 and 24 h after induction of SAP. Ascitic fluid, the pancreatic index (wet weight ratio) and myeloperoxidase (MPO) levels in the pancreas were determined and histopathological findings were evaluated. The expression of intercellular adhesion molecule-1 (ICAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), NF-κB p65, and heme oxygenase-1 (HO-1) in the pancreas were estimated by immunofluorescence and western blot, respectively.
  
  
  RESULTS
  ATL rats had lower serum levels of TNF-α, IL-1β, and IL-6 (P<0.01), PLA2 (P<0.05), and amylase levels (P<0.05) studied as compared with the SAP group. The pancreatic index in the ATL group decreased only at 24 h as compared with the SAP group (P<0.05). The histopathological findings and MPO levels in the pancreas significantly decreased in the ATL group as compared to the SAP group (P<0.05 and P<0.01, respectively). Immunofluorescence and western blot showed that ATL attenuated the expression of NF-κB p65, ICAM-1 and PECAM-1 in the pancreas, and increased the expression of HO-1 in SAP animals.
  
  
  CONCLUSIONS
  We demonstrated that RAI with ATL attenuated the severity of experimental SAP, maybe achieved by improving the expression of HO-1, and down-regulating the NF-κB signaling pathway, with decreased expression of ICAM-1 and PECAM-1 and reduced generation of pro-inflammatory cytokines.
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Fajing
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Yangyun
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Yuepeng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Zhejiang Provincial Top Key Discipline in surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejaing Province, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Surgery, Clinical Sciences Lund, Lund University and Lund University Hospital, Lund, Sweden.
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D007261:Infusions, Intra-Arterial; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D044045:Lipoxins / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D054467:Phospholipases A2 / Q000097:blood; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D044045:Lipoxins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; D018799:Intercellular Adhesion Molecule-1; D013656:Taurocholic Acid; D009195:Peroxidase; D051547:Heme Oxygenase-1; D054467:Phospholipases A2; D000681:Amylases; D001241:Aspirin