Serum Paraoxonase 1 Activity And Lipid Peroxidation Levels In Patients With Obstructive Sleep Apnea Syndrome

【Background】obstructive sleep apnea syndrome(OSAS) is a common sleep breathing disorder. OSAS affect people's sleep quality, and also be involved in the development of systemic diseases. Epidemiological studies have shown that OSAS is closely related with cardiovascular disease, which can increase hypertension, coronary heart disease, arrhythmia and stroke morbidity and mortality, so OSAS is an independent risk factor of cardiovascular disease . However, the pathogenesis of the cardiovascular complications of OSAS, is not entirely clear. Previous studies that OSAS patients with recurrent apnea during sleep at night followed hypoxia and hypercapnia, leading to autonomic nervous regulation disorders, endothelial dysfunction, hemodynamic change, fibrinolytic system dysfunction, and chronic inflammation may be involved in cardiovascular disease mechanisms, but still not comprehensive enough to explain its pathogenesis. Atherosclerosis is the pathophysiological basis of cardiovascular disease. Antioxidant capacity and lipid peroxidation play an important role in the process of atherosclerosis formation and development. Studies show that the decrease in antioxidant capacity and lipid peroxidation enhanced is a risk factor of atherosclerosis. Therefore, antioxidant capacity and lipid peroxidation levels of OSAS Patients has received increased attention. However, the presence of OSAS patients decreased antioxidant capacity and increased lipid peroxidation level, are still controversial. Paraoxonase 1 (PON1), an antioxidant enzyme carried by high-density lipoprotein (HDL), exerts a protective effect against oxidative damage of cells and lipoproteins, inhibiting the low density lipoprotein (LDL) oxidative modification and reducing lipid peroxidation, has anti-atherosclerosis role. Many studies have shown that PON1 activity may reflect the in vivo antioxidant capacity. Low PON1 activity as an independent risk factors for cardiovascular disease. Malondialdehyde (MDA) is a product of lipid peroxidation, free radical induced lipid oxidation product a series of compounds including reactive carboxyl, among which MDA is the most abundant, and it is relatively stable. MDA concentration reflects the level of lipid peroxidation and indirectly reflects the in vivo antioxidant capacity. Therefore, measurement of MDA is widely used as an indicator of lipid peroxidation.【Objective】To observe the changes of Lipid levels, PON1 activity, MDA concentration in OSAS patients , to evaluate antioxidant capacity and lipid peroxidation level in patients with OSAS. further to explore the potential pathogenic mechanisms of cardiovascular disease and to provide a theoretical basis for reducing the incidence of cardiovascular disease in patients with OSAS.【Method】73 patients with OSAS in our hospital (66 man and 7 women,mean age 46.2±10.5 years) and 20 age- and sex-matched controls (mean age 45.7±11.2 years) were studied. All patients were non-smokers and non-diabetics, and they did not change exercise habits or medication during the study. Subjects with a history of ischemic heart, cerebrovascular, renal, thyroid, psychiatric or infectious diseases were excluded. each subject gave informed consent. The patients with OSAS were divided into mild OSAS group(n = 18) , moderate OSAS group(n = 20)and severe OSAS group(n = 35) according to the apnea hypopnea index (AHI). All relevant indicators of sleep apnea were monitored by polysomnography. The serum levels of oxidized low density lipoprotein (ox-LDL) were assayed by enzyme-linked immunosorbent assay (ELISA), serum PON-1 activity was determined using phenyl acetate and MDA concentration were measured by thiobarbituric acid method.【Results】moderate and severe OSAS group serum triglyceride (TG) levels (2.2±1.6) mmol / L and (2.0±0.7) mmol / L were higher than the control group (1.1±0.6) mmol / L ( p <0.01). mild, moderate and severe OSAS patients serum High-density lipoprotein (HDL) levels (1.03±0.22) mmol / L, (1.01±0.21) mmol / L and (0.92±0.26) mmol / L were lower than the control group (1.25±0.32) mmol / L (p <0.01), respectively. Mild, moderate and severe OSAS group serum Ox-LDL levels (0.56±0.06) mmol / L, (0.76±0.09) mmol / L and (0.91±0.13) mmol / L were higher than the control group (0.36±0.09) mmol / L (p <0.01). Mild, moderate and severe OSAS patients serum PON1 activity (143.91±29.53) U / L, (121.53±25.83) U / L and (103.24±24.76) U / L were lower than the control group (164.22±34.67) U / L (p <0.05). PON-1 activity also differed significantly between the 3 OSAS groups(p<0.05), decreasing with the severity of OSAS. Mild, moderate and severe OSAS patients, MDA levels (4.52±0.23) umol / L, (4.63±0.36) umol / L and (4.88±0.28) umol / L were higher than the control group (3.93±0.32) umol / L (p <0.01). Correlation analysis showed that PON1 activity was negatively correlated to apnea-hypopnea index (AHI), and that was positive correlated to MinSaO2;Ox-LDL levels and MDA concentration were both positive correlated with AHI, and that were negatively correlated to MinSaO2;Ox-LDL levels and MDA concentration were both negatively correlated to PON1 activity. 20 patients with severe OSAS after 3 months nCPAP treatment, serum Ox-LDL levels were decreased (0.71±0.11) mmol / L vs (0.86±0.07) mmol / L (p <0.05), serum PON1 activity was significantly increased (110.84±11.02) U / L vs (102.69±10.02) U / L (p <0.01), serum MDA concentration was significantly decreased (4.44±0.35) umol / L vs (4.82±0.30) umol / L (p <0.01).【Conclusion】1. Decreased serum PON1 activity indicates that the antioxidant capacity is decreased in OSAS patients.2. Increased serum ox-LDL levels and MDA concentration indicates that OSAS patients with increased lipid peroxidation.3. The changes of serum PON1 activity, ox-LDL levels and MDA concentration were correlated with AHI and MinSaO2, and that is partially reversed by nCPAP treatment, suggesting that the decreased antioxidant capacity and lipid peroxidation is mainly caused by OSAS.4. nCPAP treatment can increase serum PON1 activity and decrease concentration MDA and ox-LDL levels, indicating that nCPAP therapy can improve sleep respiratory function, but also improve the antioxidant capacity and reduce lipid oxidation in patients with OSAS .