【作者】 张晓宁；

【导师】 平芬； 牛占丛；

【作者基本信息】 河北医科大学 ， 内科学， 2009， 硕士

【摘要】 目的:通过检测阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)及阻塞性睡眠呼吸暂停低通气综合征合并高血压(obstructive sleep apnea-hypopnea syndrome associated hypertension ,OSAHS+HT)患者血清过氧化氢酶(catalase,CAT)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)、脂质过氧化( lipid peroxidation , LPO )水平的变化,以丙二醛(malonaldehyde,MDA)的浓度代表脂质过氧化水平,研究三者与OSAHS及OSAHS+HT的相关性,旨在探讨OSAHS及OSAHS+HT患者体内氧化抗氧化变化,及三者在OSAHS及OSAHS+HT的病因、发病机制及病情进展中的作用。方法:随机选择OSAHS患者45例(均为男性),均经多导睡眠图(polysomnography, PSG)监测确诊,OSAHS的诊断依据中华医学会呼吸病学分会睡眠呼吸疾病学组制定的诊断标准[1],其中单纯OSAHS患者24例,年龄34～57(45.16±7.05)岁,体重指数22.72～34.29(28.36±2.82)kg/m2。OSAHS+HT患者21例,年龄29～63(49.95±9.08)岁,体重指数22.6～34.29(28.76±3.55)kg/m2,符合OSAHS诊断标准,并达到《中国高血压防治指南》[2]高血压诊断标准,高血压发生晚于OSAHS,且排除肾源性、内分泌性等因素引起的继发性高血压;对照组23例(均为男性),年龄29～64(47.00±10.98)岁,体重指数21.89～33.46(27.15±2.67)kg/m2,经询问病史及行Stardust便携式睡眠监测仪初筛检查,排除OSAHS。三组间年龄和体重指数无显著性差异(均p>0.05),并除外吸烟、饮酒、饮食及药物等干扰因素。所有入选对象均除外各种急慢性感染、肝肾疾病、风湿免疫疾病、脑血管疾病、恶性肿瘤、糖尿病、冠心病等。所有入选者在睡眠呼吸监测结束,晨醒5分钟内抽取空腹肘静脉血4ml,采用可见光分度法测定过氧化氢酶,比色法测定谷胱甘肽过氧化物酶,硫代巴比妥酸(TBA)法测定丙二醛。并记录有关的监测指标,包括睡眠呼吸暂停低通气指数(apnea hypopnea index,AHI)、血氧饱和度(SaO2)<90%时间占总睡眠时间百分比、睡眠呼吸障碍事件总时间占总睡眠时间百分比、睡眠呼吸障碍事件时最低SaO2及平均最低SaO2、睡眠呼吸障碍最长时间。比较正常对照组、OSAHS、OSAHS+HT三组间CAT、MDA、GSH-PX水平,三组间CAT、MDA、GSH-PX比较采用方差分析,两两比较采用SNK-q检验。OSAHS与OSAHS+HT患者的睡眠呼吸监测指标比较采用t检验,并将OSAHS、OSAHS+HT患者血清CAT、MDA、GSH-PX水平与睡眠呼吸监测指标进行直线相关分析。结果:1.正常对照组、OSAHS组、OSAHS+HT组血清CAT、GSH-PX、MDA比较。1.1血清CAT活性:正常对照组为62.33±7.28U/ml,OSAHS组为53.13±5.54 U/ml,OSAHS+HT组为47.61±6.58 U/ml。与正常对照组比较,OSAHS组及OSAHS+HT组CAT活性均降低,OSAHS+HT与OSAHS比较CAT活性降低更明显,均具有统计学差异(p<0.01)。1.2血清GSH-PX活性(酶活力单位U):正常对照组为118.82±24.47U,OSAHS组为98.73±20.58U,OSAHS+HT组为84.86±14.58 U;与正常对照组比较,OSAHS组及OSAHS+HT组GSH-PX活性均降低,OSAHS+HT与OSAHS比较GSH-PX活性降低更明显,均具有统计学差异(p<0.01)。1.3血清MDA浓度:正常对照组为4.13±0.44nmol/L,OSAHS组为5.66±0.87 nmol/L,OSAHS+HT组为6.22±0.82 nmol/L;与正常对照组比较,OSAHS组及OSAHS+HT组MDA浓度均升高,OSAHS+HT与OSAHS比较MDA浓度升高更明显,均具有统计学差异(p<0.01)。2. OSAHS+HT与OSAHS两组睡眠呼吸监测指标比较: AHI、SaO2<90%时间占总睡眠时间百分比、睡眠呼吸障碍事件总时间占总睡眠时间百分比升高,均具有统计学差异(t分别为3.4,2.32,2.26;p <0.01,p<0.05,p<0.05);睡眠呼吸障碍事件时最低SaO2、平均最低血氧饱和度均降低,且差异具有显著性,(t分别为2.38,2.21;p<0.05,p<0.05);而睡眠呼吸障碍最长时间在两组间无统计学差异(t=1.36,p>0.05)。3.血清CAT、GSH-PX、MDA水平分别与OSAHS及OSAHS+HT患者睡眠呼吸监测各项指标行直线相关分析:血清CAT、GSH-PX水平分别与OSAHS组、OSAHS+HT组的AHI、SaO2<90%时间占总睡眠时间百分比、睡眠呼吸障碍事件总时间占总睡眠时间百分比呈负相关。与睡眠呼吸障碍事件时最低SaO2,平均最低血氧饱和度呈正相关,与睡眠呼吸障碍最长时间无相关性。血清MDA水平分别与OSAHS组、OSAHS+HT组的AHI、SaO2<90%时间占总睡眠时间百分比、睡眠呼吸障碍事件总时间占总睡眠时间百分比呈正相关。与睡眠呼吸障碍事件时最低SaO2,平均最低血氧饱和度呈负相关,与睡眠呼吸障碍最长时间无相关性。结论:1.除外年龄、体重指数等相关因素的影响,并排除吸烟、饮酒、饮食及药物等干扰因素,OSAHS及OSAHS+HT患者血清MDA较正常对照组水平均升高,血清CAT、GSH-PX水平在两组患者较正常对照组均降低,说明OSAHS患者无论是否合并高血压,均存在氧化应激及氧化损伤。OSAHS患者的氧化应激的发生是独立于或先于高血压的发生而发展的。2. CAT、GSH-PX水平在OSAHS+HT患者较OSAHS患者明显降低,MDA水平在OSAHS+HT患者较OSAHS患者明显增高,说明氧化抗氧化失衡所造成的损伤在OSAHS+HT患者中更明显,氧化应激可能为OSAHS患者发生高血压的原因之一。3. OSAHS+HT与OSAHS两组睡眠呼吸监测指标比较显示病情更严重,缺氧更明显。4. MDA与AHI、SaO2<90%占总睡眠时间的百分比、睡眠呼吸障碍事件总时间占总睡眠时间百分比呈正相关,与睡眠呼吸障碍事件时最低SaO2、平均最低SaO2呈负相关。表明MDA随OSAHS及OSAHS+HT患者的病情及缺氧的加重而升高。而CAT及GSH-PX与AHI、SaO2<90%占总睡眠时间的百分比、睡眠呼吸障碍事件总时间占总睡眠时间百分比呈负相关,与睡眠呼吸障碍事件时最低SaO2及平均最低SaO2呈正相关,表明CAT、GSH-PX随OSAHS及OSAHS+HT患者的病情及缺氧的加重而降低。在OSAHS及OSAHS+HT患者体内存在氧化抗氧化失衡,这种失衡在OSAHS+HT患者体内更明显,CAT、GSH-PX、MDA在阻塞性睡眠呼吸暂停低通气综合征患者血中含量的变化可反映病情的严重程度,了解氧化应激的程度,可指导OSAHS的早期治疗及改善其预后。更多还原

【Abstract】 Objectives: To investigate the serum catalase (CAT)、glutathione peroxidase(GSH-PX)、lipid peroxidation(LPO) levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) without complications and in those with obsturctive sleep apnea-hypopnea syndrome associated hypertension (OSAHS+HT). The concentration of malonaldehyde(MDA) represent the LPO level. To evaluate the relationship between the three biochemical parameters and OSAHS and OSAHS+HT in order to explore the change of oxidant stress in patients with OSAHS and OSAHS+HT. To study the role of serum CAT, GSH-PX, LPO levels in the pathogenesis and progress of OSAHS and OSAHS+HT.Methods: 45 males with OSAHS were included randomly in the study , who were made a diagnosis by using polysomnography (PSG) ,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 subgroups: 24 OSAHS patients without complications (age=45.17±7.05,BMI=28.36±2.82kg/m2)and 21 OSAHS+HT patients(age=49.95±9.08,BMI=28.76±3.55 kg/m2), Occurrence of hypertension was later than that of OSAHS in patients with OSAHS+HT. Other secondary hypertension (such as renovascular and endocrinic hypertension) were excluded in OSAHS+HT patients. There are 23 males in control subjects (age=47.00±10.98,BMI=27.15±2.67 kg/m2),who were excluded OSAHS and HT, there are no significant differences in ages and BMI among control, OSAHS and OSAHS+HT subjects. Smoking, drinking, diets, drugs and other disturbance factors were excluded in this study. All observed subjects in this study were excluded infection ,Liver and nephridium disease ,rheumatic disease,cerebrovacular,malignancy diabetes mellitus,coronary heart disease and other diseases which can affect the serum catalase, glutathione peroxidase, lipid peroxidation levels .Fasting venous blood were obtained from all observed subjects after sleep-breathing monitoring within the following 5 minutes in the next morning. The serum catalase level were measured by visible radiation method , the serum GSH-PX level were detected by colorimetric method, The MDA were detected by thibabituric acid, respectively.and record the sleep-breathing parameters ,including apnea hypopnea index (AHI) , percentage of sleep time below 90% oxygen saturation (SaO2﹤90%), percentage of sleep time the total duration of apnea/hypopnea,the lowest SaO2 ,average lowest SaO2 and the longest duration of apnea/hypopnea.Differences in serum catalase、glutathione peroxidase、malonaldehyde among three groups were assessed by using one-way analysis of variance and further multiple comparisons were performed with SNK-q test. Sleep-breathing parameters of patients with OSAHS without complications were compared with those of patients with OSAHS+HT by using student’s two- tailed t test. Furthermore, linear correlations were performed between three biochemical parameters and sleep-breathing parameters of patients with OSAHS and OSAHS+HT, respectively.Results: 1. the serum catalase、glutathione peroxidase、malonaldehyde levels:1.1 the serum catalase level:in control subjects were 62.33±7.28U/ml, in patients with OSAHS were 53.13±5.54 U/ml ,in patients with OSAHS+HT were 47.61±6.58 U/ml.1.2 the serum GSH-PX level: in control subjects were118.82±24.47U, in patients with OSAHS were 98.73±20.58U,in patients with OSAHS+HT were 84.86±14.58 U.1.3 the MDA concentration: in control subjects were 4.13±0.44 nmol/L, in patients with OSAHS were 5.66±0.87 nmol/L,in patients with OSAHS+HT were 6.22±0.82 nmol/L.The serum CAT、GSH-PX level were lower, serum MDA concentrations were higher in patients with OSAHS compared with those in control subjects. There were statistical significances. There were similar results in patients with OSAHS+HT compared with those in control subjects and in patients with OSAHS+HT compared with OSAHS patients(p<0.01, respectively).2. Compared with OSAHS patients, both AHI and percentage of sleep time below 90% oxygen saturation (SaO2<90%) and percentage of sleep time the total duration of apnea/hyponea were higher in OSAHS+HT patients (t=3.4,2.32,2.26;p <0.01,p<0.05,p<0.05), both the lowest SaO2 and average the lowest SaO2 were lower in OSAHS+HT patients (t=2.38,2.21;p<0.05,p<0.05). But there were no differences in the longest duration of apnea/hypopnea between two groups(t=1.36 ,p>0.05).3. The linear correlations were found between three biochemical parameters and sleep-breathing parameters in patients with OSAHS and OSAHS+HT as follows: The serum MDA levels were correlated positively with AHI、percentage of sleep time SaO2<90%、percentage of sleep time the total duration of apnea/hyponea both in OSAHS and OSAHS+HT patients ,were correlated negatively with the lowest SaO2 and average the lowest SaO2. The correlations were not found between the longest dutation of apnea/hypopnea and MDA. The correlations between serum CAT、GSH-PX and sleep-breathing parameters were not as same as those of MDA evels , were correlated negatively with AHI、percentage of sleep time SaO2<90%、percentage of sleep time the total duration of apnea/hyponea both in OSAHS and OSAHS+HT patients, were correlated positively with the lowest SaO2 and average the lowest SaO2. And there were no correlations with the longest dutation of apnea/hypopnea.Conclusions: 1. Despite controlling for age, BMI and excluding disturbance factors such as smoking, drinking, diets and drugs, the resum MDA concentrations in patients with OSAHS and OSAHS+HT were higher than those in control subjects. Both the rusum CAT、GSH-PX levels in patients with OSAHS and OSAHS+HT were lower than those in control subjects,which indicated that there are oxidative stress and oxidative damage in OSAHS patients no matter with or without hypertension, and oxidative damage happened independent of , and possibly prior to hypertension.2. The serum CAT and GSH-PX levels in patients with OSAHS+HT was lower than those in patients with OSAHS. The serum MDA contents in patients with OSAHS+HT was higher than those in patients with OSAHS. The damage caused by the imbalance of oxidative /anti- oxidative was more obvious in patients with OSAHS+HT,oxidative stress may be one of the reasons caused hypertension in OSAHS patients.3. compared with sleep-breathing parameters, the severity and degree of hypoxemia in patients with OSAHS+HT were more seriously than OSAHS patients.4. The resum MDA levels were correlated positively to both AHI , percentage of sleep time SaO2<90% and percentage of sleep time the total duration of apnea/hyponea . The resum MDA level were correlated negatively to both the lowest SaO2 and average the lowest SaO2 . which showed a strong correlation between MDA increasing with the degree of hypoxemia. And indicated that there was a strong correlation between the change of MDA and the severity of OSAHS and OSAHS+HT.CAT、GSH-PX levels were correlated negatively to AHI and SaO2<90% and percentage of sleep time the total duration of apnea/hyponea ,the resum CAT、GSH-PX levels correlated positively to the lowest SaO2 and average the lowest SaO2 , which showed a strong correlation between CAT、GSH-PX reducing and the degree of hypoxemia. And the severity of OSAHS and OSAHS+HT.Our study demonstrated the change of oxidative /anti- oxidative imbalance in patients with OSAHS and OSHAS+HT,and it is more obvious in patients with OSHAS+HT.The information of the severity of sleep disordered breathing and the degree of oxidative stress can be obtained by measuring the change of the three biochemical parameters, which has important value to advice the early treatment and to improve the prognosis.更多还原