Study On The Mechanism Of Vascular Endothelium Impairment In Obstructive Sleep Apnea Syndrome

PartⅠThe mechanism of vascular endothelium impairment in a mouse chronic intermittent hypoxia modelObjective To explore the changes of vascular endothelial function in a mouse chronic intermittent hypoxia model.Method On the base of chronic intermittent hypoxia model we established before, the method of nitric acid reductase and chemical colorimetry were used to detect the levels of nitric oxide (NO) and epithelial nitric oxide synthase (eNOS) activity in mice blood serum respectively, which experienced intermittent hypoxia for 1,2,3,4 and 6 weeks. The changes of NO levels and eNOS activity were observed. At the end of experiment, the endothelial structure of pulmonary artery by transmission electron microscope were observed.Result (1) The CIH mice displayed lower serum NO levels as early as week 1 after initiation of CIH (p>0.05). At Week 2, the mean±SD serum NO levels was (78.96±9.93)μmol/L in CIH mice compared to (106.31±19.06)μmol/L in UC mice (p<0.05), followed by statistically significant progressive decrease (p<0.05 or p<0.01).The CIH mice displayed lower serum eNOS activity as early as week 1(CIH 22.26±2.96 &UC 25.58±3.47 U/ml,p<0.05), followed by significant progressive decrease at week 2 (p<0.01).The difference had statistical significance between CIH groups and UC groups(p<0.05 or p<0.01). (2) At week 6, electron microscopic changes of the endothelial structure of pulmonary artery of mouse including the endothelial cells apophy to lumens, edema, mitochondria distension, cristae collapse, vacuolar degeneration and chromatin condensation, was observed in endothelial cells.Conclusion The CIH mice displayed lower serum NO levels and eNOS activity gradually over CIH time. The endothelial structure of pulmonary artery of mouse was changed.PartⅡThe mechanism of vascular endothelium impairment in patients with obstructive sleep apnea-hyponea syndromeObjective To explore the changes of vascular endothelial function in patients with obstructive sleep apnea-hyponea syndrome (OSAHS).Method A total of 73 consecutive patients with snoring were examined by overnight polysomnography (PSG) in our sleep center between June 2008 and February 2009.Based on the assessment of the apnea-hypopnea index (AHI), these patients were divided into three groups: primary snoring group (AHI<5/h, n=12), and the mild-moderate (AHI 5-40/h, n=36) & severe (AHI>40/h, n=25) OSAHS groups. The levels of NO, body mass index (BMI)and PSG parameters (lowest pulse oxygen saturation L-SaO2, the time of oxygen saturation<90%, mean pulse oxygen saturation M-SaO2oxygen and apnea-hypopnea index AHI) and incidence of hypertension were compared between the primary snoring group vs. OSAHS patients with varying severities and the correlations between incidences of hypertension with PSG parameters were evaluated by multivariate stepwise regression analysis.Result There was no significant difference in age or BMI between three groups (p>0.05), whereas nocturnal hypoxia index were significantly higher in the severe OSAHS patients than the other groups (p<0.01).The incidences of hypertension progressive increased and the levels of serum NO decreased significantly (p<0.01) as the severity of OSAHS aggravated. The linear regression further revealed that NO levels correlated positively with AHI and the time of oxygen saturation<90% (r=-0.83,-0.54 respetively,p<0.01), whereas negatively correlated with M-SaO2 and L-SpO2 (r=0.48,0.52 respetively,p<0.01).Conclusion The incidence of hypertension progressive increased as the severity of OSAHS aggravated. The levels of serum NO decreased as the severity of OSAHS aggravated, which is one of the possible causes in the development of systemic hypertension.