| Objective: The study aimed to research the effects of OSAHS upon the expression of nuclear NF-κB P65 and the concentration of inflammatory cytokines IL-6 and Inflammatory inhibitory factor IL-10 in the myocardium and the changes of myocardial structure,and to explore the changes of the-above biomarkers of OSAHS rabbits after treated with mandibular advancement device(MAD)by setting up the animal model of New Zealand white rabbits with obstructive sleep apnoea-hypopnea syndrome(OSAHS).The above results can used to investigate the possible inflammatory mechanisms of cardiovascular disease,which provided corresponding theoretical base for the pathogenesis of myocardium injury induced by OSAHS and the influence on myocardium of OSAHS with the treatment of MAD.Methods: 1.Animals groupedEighteen male New Zealand white rabbits,aged six months old were randomly divided into three groups : group OSAHS,group MAD and control group respectively.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 2 ml 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.Sleep in supine positionAll subjects were given 10% chloral hydrate through mouth by 5 ml/kg-6 ml/kg and slept 2 hours-4 hours every morning in supine position during the next eight weeks.4.Collection and disposal of samplesAfter observating 8 weeks,the myocardium specimens were taken,part of myocardium tissue was fixed in 4% polyformaldehyde and the remaining myocardium tissue was stored in liquid nitrogen and preserved at-80oC.Observed the myocardial interstitial fibrosis which had been stained by sirius red under polarized light and detected the relative expression of mRNA and protein of nuclear factor kappa B(NF-κB),and the expression of IL-6 and IL-10 by molecular biology methodResults:1.The general situation of animalsWhile sleeping in supine position,animals of group OSAHS had obvious,uneven snore.Rabbit in group MAD were stable,except for light snore in a few animals,rabbit of control group breathed regularly and smoothly.2.CT scans of upper airwayThe CT results showed that the upper airway cross-sectional diameter and the sagittal space in 1/4 point,1/2 point and 3/4 point of soft palate were decreased significantly in Group OSAHS compared with group MAD and control group(P<0.05),and there was no significant difference between group MAD and the control group(P>0.05).3.PSG recordingsThe PSG results indicated that apnoea hypopnea index increasedsignificantly and the average blood oxygen saturation and minimal oxygensaturation decreased significantly in group OSAHS compared with groupMAD and control group(P<0.05),and there was no significant differencebetween group MAD and the control group(P>0.05).4.Relative expression of NF-κB P65 protein in the nuclear of myocardiumThe relative expression of NF-κB P65 protein in myocardium in group OSAHS,group MAD and control group were 1.11±0.04,0.62±0.03,0.57±0.04 respectively.The data in group OSAHS was significantly higher than the group MAD and control group(P<0.05),while there was no significant difference between group MAD and control group(P>0.05).5.Relative expression of NF-κB P65 mRNA in the nuclear of myocardium.The relative expression of NF-κB P65 mRNA in myocardium in group OSAHS,group MAD and control group were 1.54±0.08,1.07±0.08,1.05±0.06 respectively.The data in group OSAHS was significantly higher than group MAD and control group(P<0.05),while there was no significant difference between group MAD and control group(P>0.05).6.The expression of IL-10 and IL-6 in the myocardium.The concentration of IL-10 in myocardium in group OSAHS,group MAD and control group were 57.68±2.16 pg/ml,50.78±1.44 pg/ml,49.77±2.24 pg/ml respectively.The data in group OSAHS was significantly higher than group MAD and control group(P<0.05),while there was no significant difference between group MAD and control group(P>0.05).The concentration of IL-6 in myocardium in group OSAHS,group MAD and control group were 68.43±1.11 pg/ml,38.25±0.94 pg/ml,37.22±1.22 pg/ ml,respectively.The data in group OSAHS was significantly higher than group MAD and control group(P<0.05),while there was no significant difference between group MAD and control group(P>0.05).7.Collagen fibrosis in apical tissueResults of the observation under polarized light microscope: collagen ratio of group OSAHS,group MAD and control group were 0.47±0.02,0.20±0.01,0.18±0.01 respectively.Collagen ratio of type I / III were 7.10±1.17,2.43±0.26,2.40±0.23 respectively.The data in group OSAHS was significantly higher than group MAD and control group(P<0.05),while there was no significant difference between group MAD and control group(P>0.05).Conclusion:1.OSAHS can cause the activation of NF-κB which can increase the concentration of its own and downstream inflammatory factors in myocardium.The elevation of these inflammatory indicators may accelerate the development of myocardial fibrosis.2.Treating OSAHS with mandibular advancement device(MAD)can reduce the activation of NF-κB which decreased the the concentration of inflammation related products,which plays a significant role in preventing of myocardial fibrosis. |
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