Role of heparin on serum VEGF levels and local VEGF contents in reducing the severity of experimental severe acute pancreatitis in rats

Scand J Gastroenterol. 2012 Feb;47(2):237-44. doi: 10.3109/00365521.2011.647063. Epub 2012 Jan 3.

Abstract

Objective: The aims of this study were to examine the effects of prophylactic heparin treatment during taurocholate-induced pancreatitis in rats and its impact on serum VEGF levels and local VEGF contents within the pancreas.

Methods: Severe acute pancreatitis (SAP) was induced by injecting 4% sodium taurocholate into the pancreatic duct. Heparin at a dose of 150 IU/kg s.c. was administered 30 min before the operation. The rats were sacrificed 1 h, 3 h, 6 h and 12 h (n = 5 per time point) after the onset of pancreatitis. The severity of pancreatitis, serum VEGF levels and local VEGF contents were evaluated with and without heparin pretreatment.

Results: The serum VEGF levels increased at an early phase of pancreatitis, and the highest level was found at 12 h after inducing pancreatitis. The gray value of the local VEGF showed a remarkable increase from the onset of the pancreatitis. However, the gray value of VEGF did not show an increase over time but maintained a high level during the entire process. Prophylactic heparin treatment significantly improved the morphologic changes, myeloperoxidase (MPO), TNF-α and malondialdehyde (MDA) activities. Meanwhile, it decreased the serum VEGF levels and the contents of VEGF within the pancreatic tissue.

Conclusions: The present study suggests that prophylactic heparin ameliorates the severity of taurocholate-induced pancreatitis via its anti-inflammatory properties. These protective effects may be partly due to decreasing serum VEGF levels and VEGF contents within the pancreas.

MeSH terms

  • Acute Disease
  • Amylases / blood
  • Animals
  • Anticoagulants / therapeutic use*
  • Glutathione / metabolism
  • Heparin / therapeutic use*
  • Leukocytes
  • Male
  • Malondialdehyde / metabolism
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy*
  • Pancreatitis / metabolism*
  • Pancreatitis / pathology
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Taurocholic Acid
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / metabolism*
  • Water / metabolism

Substances

  • Anticoagulants
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Water
  • Malondialdehyde
  • Taurocholic Acid
  • Heparin
  • Peroxidase
  • Amylases
  • Glutathione