Study On The Correlation Between Plasma GSH/GSSG,Serum NADPH/NADP~+ And OSAHS,OSAHS Associated Hypertension

Objectives: To investigate the plasma reduced glutathione (GSH) , oxidizided glutathione(GSSG) and the serum reduced coenzyme II(NADPH),oxidized coenzyme II(NADP+) level in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) without compilcations and in those with obsturctive sleep apnea-hypopnea syndrome associated hypertension (OSAHS+HT). To study the correlation between plasma GSH/GSSG ratio, serum NADPH/NADP+ ratio and OSAHS ,OSAHS+HT in order to explore the role in the occurrence of OSAHS and OSAHS+HT.Methods: Thirty-nine males with OSAHS were included randomly in the study, who were made a diagnosis by using polysomnography. The standard of diagnosis according to diagnostic standard formulated by group of sleep-breath disease to Chinese Medical Association. All patients with OSAHS were divided into two groups: 20 OSAHS patients without complications (age= 42.90±7.60, BMI=27.60±2.67kg/m2) and 19 OSAHS+HT patients (age=48.37±9.44, BMI=29.40±3.40kg/m2). The standard of hypertension diagnosis was accorded to clinical diagnostic standard formulated by WHO/ISH in 1979. Occurrence of hypertension was later than OSAHS in patients with OSAHS+HT. Other secondary hypertension (such as renovascular and endocrinic hypertension) were excluded in OSAHS+HT patients. There were 19 men in control subjects (age=44.95±10.50, BMI=27.26±4.30kg/m2), who were excluded OSAHS. There were no significant differences in age and BMI among control subjects, OSAHS and OSAHS+HT. Smoking, drinking, diets, drugs and other disturbance factors were excluded in this study. All observed subjects in this study were excluded cerebrovascular disease, chronic respiratory disease, ischemic heart disease, secondary hypertension, diabetes mellitus, liver and nephridium disease, autoimmune disease and other diseases which can affect the plasma GSH, GSSG and serum NADPH, NADP+ level. Fasting venous blood were obtained from all observed subjects after sleep-breath monitoring within the following 5 minutes in the next morning. Plasma GSH, GSSG and serum NADPH, NADP+ level were measured by spectrophotography and ELISA and recorded the sleep-breath parameters, including apnea hypopnea index(AHI), percentage of sleep time below 90% oxygen saturation(CT90%), oxygen desaturation index (ODI), arousal index(ArI). Plasma GSH level, GSSG level, GSH/GSSG ratio and serum NADPH level, NADP+ level, NADPH/NADP+ ratio were compared respectively among control subjects, OSAHS and OSAHS+HT patients. Sleep-breath parameters of the later two groups were also compared respectively. Furthermore, the correlations were analyzed between GSH/GSSG, NADPH/ NADP+ ratio and sleep-breath parameters in OSAHS and OSAHS+HT patients, respectively.Results: 1.Plasma GSH level, GSSG level, GSH/GSSG ratio and serum NADPH level, NADP+ level, NADPH /NADP+ ratio were 246.91±14.76 mg/L, 14.64±5.57 mg/L, 21.07±13.71, 2.72±0.27 mg/L, 0.61±0.14 mg/L, 4.61±1.03 in control subjects, were 237.20±16.23 mg/L, 27.96±12.30mg/L, 11.40±7.36, 2.17±0.67 mg/L, 1.00±0.14mg/L, 2.26±0.85 in OSAHS patients and 222.53±14.09mg/L, 40.16±8.03mg/L, 5.81±1.44, 1.52±0.38 mg/L, 1.45±0.17 mg/L, 1.07±0.31 in OSAHS+HT patients, respectively. Plasma GSSG and serum NADP+ were both higher in OSAHS patients than control subjects and there were statistical significances (P<0.01). But plasma GSH level, GSH/GSSG ratio and resum NADPH level, NADPH/NADP+ ratio were all lower (P<0.05, P<0.05, P<0.01, P<0.01). There were similar results in patients with OSAHS+HT compared with control subjects (P<0.01) and in patients with OSAHS+HT compared with OSAHS patients (P<0.01). 2. Compared with OSAHS patients, the AHI, CT90%, ODI, and ArI were all higher in OSAHS+HT patients (t=2.048, P<0.05; t=2.110, P<0.05; t=2.282, P<0.05; t=2.366, P<0.05). 3. The plasma GSH/GSSG ratio were correlated positively with serum NADPH/NADP+ ratio in both OSAHS and OSAHS +HT patients(r=0.795, P<0.01; r=0.600, P<0.01). 4.The linear correlations were found between the two factor's ratio and sleep-breath parameters in patients with OSAHS and OSAHS+HT as follows:①The plasma GSH/GSSG ratio were correlated negatively with AHI both in OSAHS and OSAHS+HT patients(r=-0.853, P<0.01; r=-0.676, P<0.01), were correlated negatively with CT90%( r=-0.687, P<0.01; r=-0.494, P<0.05), were correlated negatively with ODI (r=-0.847, P<0.01; r=-0.839, P<0.01), were correlated negatively with ArI (r=-0.495, P<0.05; r=-0.528, P<0.05).②The correlations between serum NADPH/NADP+ ratio and sleep-breath parameters were the same with plasma GSH /GSSG. NADPH/NADP+ ratio in both OSAHS and OSAHS+HT pantients were correlated negatively with AHI(r=-0.687, P<0.01; r=-0.494, P<0.05), were correlated negatively with CT90%(r=-0.799, P<0.01; r=-0.601, P<0.01), were correlated negatively with ODI(r=-0.847, P<0.01; r=-0.839, P<0.015), were correlated negatively with ArI(r=-0.646, P<0.01; r=-0.665, P<0.01).Conclusions: 1.Despite controlling for age, BMI and excluding disturbance factors such as smoking, drinking, diets and drugs, and effect of diseases, the plasma GSH/GSSG ratio and serum NADPH/NADP+ ratio in patients with OSAHS and OSAHS+HT were both lower than those in control subjects. Furthermore, the two factor's ratio were correlated negatively with AHI,CT90%,ODI,ArI. This study indicated that there was a strong correlation between the two factors'ratio and the degree of hypoxemia in OSAHS and OSAHS+HT. 2. GSH/GSSG and NADPH/NADP+ were the important redox couples of the body. Many studys have showed that there was an increased oxidative stress in OSAHS patients. The balance of pro-oxidant and antioxidant played an important role in the occurrence and development of OSAHS. The plasma GSSG and serum NADP+ level increased in OSAHS patients , but the plasma GSH level, GSH/GSSH ratio and the serum NADPH level, NADPH/NADP+ ratio decreased , which showed that redox state changed for oxidation. The plasma GSSG and serum NADP+ level were higher in OSAHS+HT patients, and yet the plasma GSH level, GSH/GSSH ratio and the serum NADPH level, NADPH/NADP+ ratio were even lower. The sleep-breath parameters have significant differences in OSAHS and OSAHS+HT patients. These indicated that OSAHS+HT patients were more severe than OSAHS patients and the change of redox state was likely an important factor in the occurrence of hypertention. OSAHS was an independent factor to hypertention. Observing the change of redox state in OSAHS patients would be an important theoretical significance and value of appliance for the diagnosis, therapy, inspecting state of OSAHS and estimating prognosis.