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

Abstract

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