Prophylactic low-molecular-weight heparin administration protected against severe acute pancreatitis partially by VEGF/Flt-1 signaling in a rat model.

Abstract

BACKGROUND:

The present study was aimed to explore the effects and the underlying mechanism of prophylactic low-molecular-weight heparin (LMWH) treatment on taurocholate-induced severe acute pancreatitis (SAP) in a rat model.

METHODS:

Rat SAP model was induced by injection of 4% sodium taurocholate into the pancreatic duct. LMWH was applied half an hour before the induction of pancreatitis at the dose of 200 IU/kg subcutaneous injection. The rats were euthanized at 1 h, 6 h, and 12 h after taurocholate-induced SAP. The inflammatory and oxidative response markers were assessed. And the vascular endothelial growth factor (VEGF) and Fms-related tyrosine kinase 1 (Flt-1) expression were evaluated by immunohistochemistry (IHC) and western blot methods.

RESULTS:

The expression of inflammatory and oxidative response markers increased after induction of SAP. IHC and western blot results showed the VEGF and Flt-1 expression were increased in SAP group. Prophylactic LMWH administration reduced the inflammatory and oxidative response markers expression and decreased the expression of VEGF and Flt-1.

CONCLUSIONS:

This study suggested that prophylactic LMWH treatment mitigated the severity of pancreatitis in rat SAP model by anti-inflammation and oxidative response. The underlying mechanism may result from downregulating VEGF/Flt-1 signaling of LMWH in SAP rat model.

• Authors: S Li, S Zhang, R Li, S Chen, S Chang, X Chen, Y Li, X Su, T Wu, M Xu
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 39 Issue 10 Pg. 1345-1354 (Oct 2020) ISSN: 1477-0903 [Electronic] England
• PMID: 32351125 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Heparin, Low-Molecular-Weight
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Taurocholic Acid
• Flt1 protein, rat
• Vascular Endothelial Growth Factor Receptor-1

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Antioxidants (pharmacology, therapeutic use)
• Disease Models, Animal
• Heparin, Low-Molecular-Weight (pharmacology, therapeutic use)
• Male
• Pancreas (drug effects, metabolism, pathology)
• Pancreatitis (chemically induced, drug therapy, metabolism, pathology)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Taurocholic Acid
• Vascular Endothelial Growth Factor A (metabolism)
• Vascular Endothelial Growth Factor Receptor-1 (metabolism)