Hyperbaric oxygen intervention on expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in spinal cord injury models in rats

摘要

Background Hyperbaric oxygen (HBO) intervention is a main therapeutic method and the curative effect has been certified for spinal cord injury (SCI),but the mechanisms of the neuroprotective effect of HBO on SCI remain elusive.This study aimed to observe the change in expression of hypoxia-inducible factor-1α (HIF-1α） and vascular endothelial growth factor (VEGF) after SCI at different time points and to investigate the neuroprotective mechanism of HBO on SCI in rats.Methods A total of 160 adult Sprague-Dawley rats,weighing between 250 and 300 g,were randomly assigned to four experimental groups (n=40 per group).SCl group:SCl was created with a special NYU impactor of Allen's by a 25 gramcentimeter impacting energy on T10 of the spinal cord.SCI+HBO group:HBO therapy after SCI model was established.Sham operation (SH) group:only laminectomy of T10 and no impact on the spinal cord was done.SH+HBO group:HBO therapy after sham operation.The hindlimb functional recovery was evaluated using Basso,Beattie,and Bresnahan (BBB) score and the expressions of HIF-1α and VEGF were observed with fluorescent quantitation PCR and Western blotting method of six rats picked randomly from each group at different time points of 1,3,7,and 14 days after operation.Results Rats in the SCI group and SCI+HBO group were paralyzed completely after operation with BBB 0-1 score.Rats in the SH group and SH+HBO group could walk after sham operation with BBB 20-21 score.The BBB score of rats in the SCI+HBO group (4.67±1.97 and 10.83±2.23) was higher than that in the SCI group (1.83±0.75 and 6.67±2.16) at 7 and 14 days time points obviously (P ＜0.05).The expressions of HIF-1α and VEGF in the SCI group and SCI+HBO group were higher than in the SH group and SH+HBO group at any time point obviously (P ＜0.05),while the SCI+HBO group presented the least expression of HIF-1α mRNA and protein (3.82±0.41 and 0.59±0.06; 2.26±0.41 and 0.37±0.05; 1.58±0.26 and 0.29±0.05) than that in the SCI group (6.36±0.58 and 0.76±0.07; 3.55±0.47 and 0.51±0.07; 2.27±0.39 and 0.40±0.06) respectively at 3,7,and 14 days time points (P ＜0.05) with significant difference and more expression of VEGF mRNA and protein (5.83±0.77 and 0.72±0.06; 4.59±0.51 and 0.63±0.06) than that in the SCI group (3.06±0.30 and 0.48±0.07; 2.25±0.24 and 0.39±0.09) respectively at 7 and 14 days time points (P ＜0.05) with significant difference.Conclusions HBO could improve the hind limb functional recovery after SCI in rats.The elevation and duration of the expression of VEGF and the reduction of expression of HIF-1α by HBO intervention may be inversely related in the repair of damaged spinal cord and neuroprotective effect.