Effect Of A Mandibular Advancement Device Therapy On Hif-1??EPO And VEGF In Myocardia Of OSAHS Rabbits

Objective:This study aimed to research the changes of hypoxia-inducible factor-1??HIF-1??and its downstream genes Erythropoietin?EPO?and vascular endothelial growth factor?VEGF?after the rabbit model with obstructive sleep apnea-hypopnea syndrome?OSAHS?and Mandibular advancement device?MAD?were build separately,then to discuss the possible mechanism of myocardial tissue injury caused by OSAHS and the effect of mandibular forward appliance on this mechanism in the treatment of OSAHS.Methods:1.Animals groupedEighteen rabbits were assigned randomly to three groups:group OSAHS?n=6?,group MAD?n=6?and control group?n=6?.2.Animal model establishmentThe upper airway Cone beam Computer Tomography?CBCT?scanner and polysomnography were given to all animals.The soft palate muscular layer of mucosa in group OSAHS and group MAD rabbits'were injected 2ml sodium hyaluronate gel under general anesthesia,and then CBCT and polysomnography were done in group OSAHS and group MAD to assess the effect of OSAHS modeling.After the success of modeling,OSAHS rabbits in group MAD were worn mandiblular advancement device?MAD?.And CBCT and polysomnography were done in group MAD again to assess the therapeutic effect of MAD.3.Upper airway three-dimensional?3D?models establishmentThree-dimensional?3D?models from the top of soft palate to hyoid of the upper airway were build and analyzed by mimics imaging software 21.0.4.Sleep in supine positionAll subjects were given 10%chloral hydrate through mouth by 5 ml/kg-6ml/kg and slept 2 hours-4 hours every morning in supine position during the next eight weeks.5.Collection and disposal of samplesAfter observating 8 weeks,the myocardium specimens were taken and stored in liquid nitrogen and preserved at-80oC.The relative expression of mRNA and protein of HIF-1?,and the expression of EPO and VEGF were detected by molecular biology method.Results:1.The general situation of animalsThe typical symptoms of snoring and arousal were obvious during supine sleep in group OSAHS,and were relieved in group MAD.2.Measurements of Upper airway three-dimensional?3D?modelsMeasurements about 3D models of upper airway of group OSAHS exhibited reduced volume,sagittal space and cross-sectional areas than those of group MAD and control group?p<0.05?.3.PSG recordingsOSAHS models developed obvious sleep apnoea and hypopnea in supine position,with increased apnoea-hypopnea index?AHI?,decreased oxygen saturation?SaO₂%?and lowest oxygen saturation?LSaO₂??p<0.05?,but no significant difference between group MAD and control group?p>0.05?.4.Relative expression of HIF-1?protein in the nuclear of myocardiumThe relative expression of HIF-1?protein in myocardium of group OSAHS,group MAD and control group was 1.11±0.04,0.62±0.03,0.57±0.04,respectively.Group OSAHS was significantly higher than that of group MAD and control group?P<0.05?.There was no significant difference between group MAD and control group?P>0.05?.5.Relative expression of HIF-1?mRNA in the nuclear of myocardium.The relative expression of HIF-1?mRNA in group OSAHS,group MAD and control group was 1.54±0.08,1.07±0.08,respectively,and 1.05±0.06.Group OSAHS was significantly higher than the other two groups?P<0.05?.There was no significant difference between group MAD and control group?P>0.05?.6.The expression of EPO and VEGF in the myocardium.The concentration of EPO in myocardium of group OSAHS,group MAD and control group was 57.68±2.16 pg/ml,50.78±1.44 pg/ml,49.77±2.24pg/ml;The concentration of VEGF in myocardium of group OSAHS,group MAD and control group was 68.43±1.11 pg/ml,38.25±0.94 pg/ml,37.22±1.22 pg/ml.Group OSAHS was significantly higher than that of the other two groups?P<0.05?.There was no statistical significance between group MAD and control group.The difference was significant?P>0.05?.Conclusion:1.Hypoxia adaptive pathway was activated in OSAHS rabbit myocardium,which can regulate the high expression of HIF-1?and its downstream factor EPO and VEGF.2.MAD therapy could move the mandible forward and expand the airway to reduce the high expression of HIF-1?,EPO and VEGF.