The Effect Of Nuclear Factor Kappa B On Vascular Endothelial Injury In Patients With Obstructive Sleep Apnea Hypopnea Syndrome

[Background]Obstructive sleep apnea hypopnea syndrome(OSAHS) is a chronic sleep disorder with high prevalent rate,affecting multiple organs and systems mainly including cerebrocardiovascular system.Endothelial dysfunction and thus atherosclerosis(AS) may result in various cerebrocardiovascular complications,which could be lethal.The abnormal activation of NF-κB may play a key role in the initiation and progression of AS.And peripheral blood mononuclear cells(PBMC) are also involved in the process of chronic inflammation.Shedding of the vascular wall, circulating endothelial cells(CECs) can directly reflect the vascular endothelial injury with high sensitivity.It is poorly understood whether NF-κB activation in PBMC can affect the vascular endothelial apoptosis.Exploration on the issue could be beneficial for us to know the underlying mechanism of OSAHS and complications.[Objective]We investigate the NF-κB expression and inflammatory cytokines excretion,as well as the numbers and apoptosis of CECs,in order to evaluate the effect of NF-κB activation on vascular endothelial injury from patients with OSAHS.[Methods]Subjects were classed into normal,mild,moderate,severe groups(n=15, respectively) according to polysomnography(PSG).After PSG,samples of peripheral venous blood were collected,and mononuclear cells were isolated.Nuclear protein was extracted and NF-κB was measured by Western blotting.ELISA was applied to measure the levels of TNF-αand IL-6 in serum.Flow cytometry was applied to detect the numbers and apoptosis of CECs.Blood samples from ten severe cases were measured again after four weeks of CPAP.[Results]NF-κB expression was increased significantly in OSAHS group compared with controls(P＜0.05).TNF-αin serum was significantly increased in severe and moderate OSAHS compared with controls(P＜0.05).No significance was observed among severe group,mild group and controls in IL-6 concentration.The numbers and apoptosis rate of CECs were higher in severe and moderate group than in mild and control group(P＜0.05).CECs correlated positively with apnea hypopnea index(r=0.706,P＜0.001).The apoptosis rate of CECs was positively significantly correlated with AHI,NF-κB expression and TNF-αlevel;negatively correlated with LSaO₂(P＜0.05),but non-significantly correlated with IL-6(P＞0.05).CPAP could significantly reduce TNF-αexcretion,inhibit NF-κB activation and lessen endothelial apoptosis(P＜0.05,respectively).[Conclusions]Peripheral blood mononuclear cells may play an important role in vascular endothelial injury through NF-κB abnormal expression and inflammatory cytokines excretion in OSAHS patients,which was closely associated with the severity of the syndrome and night hypoxemia.CPAP could inhibit the pathophysiologic process effectively.