Bosentan protects the spinal cord from ischemia reperfusion injury in rats through vascular endothelial growth factor receptors.

Abstract

STUDY DESIGN:

Experimental study.

OBJECTIVES:

To investigate whether Bosentan, an endothelin-A/-B dual receptor antagonist, could protect neurons after spinal cord ischemia reperfusion (SCIR) injury in rats and its underlying signaling pathway.

SETTING:

Department of Neurosurgery, the Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi Province, China.

METHODS:

Sprague-Dawley rats were randomly divided into two groups, saline group (IRS, n=48) and Bosentan group (IRB, 5 mg kg(-1), n=48). After ischemia for 1 h with occlusion of the infrarenal aorta, spinal cord were reperfused for 6h, 12h, 24h, 3d, 5d, and 7d separately. Enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor (VEGF) in serum. Immunohistochemistry was performed to detect protein expression of VEGF, VEGF receptor 1 (FLT-1) and VEGF receptor 2 (FLK-1). Gene expressions of VEGF and its receptors were evaluated using the quantitative reverse transcription polymerase chain reaction.

RESULTS:

Compared with the IRS group, gene and protein expressions of VEGF, FLT-1 and FLK-1 were significantly increased (P<0.05), so was the concentration of VEGF in plasma (P<0.05). FLK-1 was expressed on spinal cord neurons.

• Authors: S Gong, Z Seng, W Wang, J Lv, Q Dong, B Yan, L Peng, X He
• Journal: Spinal cord (Spinal Cord) Vol. 53 Issue 1 Pg. 19-23 (Jan 2015) ISSN: 1476-5624 [Electronic] England
• PMID: 25179655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin Receptor Antagonists
• Sulfonamides
• Vascular Endothelial Growth Factor A
• Flt1 protein, rat
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2
• Bosentan

Topics

• Animals
• Bosentan
• Disease Models, Animal
• Endothelin Receptor Antagonists (therapeutic use)
• Gene Expression Regulation (drug effects)
• Ischemia (complications)
• Male
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury
• Spinal Cord Injuries (etiology, prevention & control)
• Sulfonamides (therapeutic use)
• Time Factors
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-1 (genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (genetics, metabolism)