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.