【作者】 张宏英；

【导师】 林其昌；

【作者基本信息】 福建医科大学 ， 内科学， 2009， 硕士

【摘要】 目的初步探讨同型半胱氨酸(homocysteine,HCY)在阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)并心血管疾病(cardiovascular diseases,CVD)的病理生理过程中的意义,进一步理解OSAHS相关性心血管疾病的发生发展机制,为寻找防治OSAHS并发症的途径提供思路。方法实验1.因打鼾在我院经多导睡眠仪行夜间7小时睡眠监测后,连续入选94例,分组如下:15例单纯鼾症组、42例单纯OSAHS组及37例OSAHS合并CVD(OSAHS+CVD)组。抽取静脉血用免疫比浊法检测血浆HCY、hs-CRP浓度,采用Olympus2700全自动生化分析仪测定血脂及血糖。对比各实验组患者间HCY、hs-CRP、血脂、睡眠呼吸参数的差异以及不同指标间的相关性。实验2.开展干预实验,从OSAHS组、OSAHS+CVD组中选择愿意接受经鼻持续气道正压通气(nasal continuous positive air pressure,nCPAP)治疗的患者,其中OSAHS组30例,OSAHS+CVD组24例,后者继续使用原有心血管药物。经3个月的nCPAP治疗,比较两组患者治疗前后的睡眠参数、HCY、hs-CRP浓度变化。运用SPSS11.5 for windows统计软件进行分析。计量资料采用单因素方差分析及协方差分析,计数资料采用R×C表χ2检验,两因素相关性研究采用Pearson相关系数进行直线回归分析,并采用逐步回归分析法进行预测因子的评价,治疗前后比较用配对t检验。P<0.05为差异有统计学意义。结果1、单纯鼾症组、OSAHS组、OSAHS+CVD组HCY值逐渐升高,差异有统计学意义[分别为(9.42±0.68)umol/L、(12.70±2.45)umol/L、(14.63±2.98)umol/L,F=15.042,P=0.000]。2、各实验组间hs-CRP水平不同(F=6.855,P=0.002),两两比较发现在OSAHS组与OSAHS+CVD组间差别有意义[(1.32±0.61)mg/L vs (2.13±1.87)mg/L,P<0.05],其余两两比较亦有显著性差别。3、各组间TC、TG、VLDL水平不同,但三组间以上各指标两两比较显示差异不全有意义。4、HCY浓度与AHI(r= 0.899、P<0.01)、RIT(r= 0.835、P<0.01)、ODI4(r= 0.760、P<0.01)、TS90%(r= 0.721、P<0.01)、最长呼吸暂停时间(r=0.532、P<0.01)、hs-CRP(r=0.542、P<0.01)呈正相关,与Minspo2(r= -0.749、P<0.01)、Meanspo2(r=-0.673、P<0.01)呈负相关,与血脂各指标相关性相对不强。5.逐步回归分析显示AHI及RIT是HCY水平的预测因素,t值分别为6.635(P=0.000)、2.381(P=0.019)。回归方程为:HCY=8.117+0.085*AHI+0.047* RIT(F=116.231,P=0.000)。6.接受nCPAP治疗的OSAHS组、OSAHS+CVD组睡眠呼吸紊乱均得到改善,两组血浆HCY浓度较同组治疗前明显下降[分别为(12.51±1.91)umol/L vs ( 10.39±1.28 ) umol/L , P<0.05 ; (14.86±2.11)umol/L vs (12.74±2.73)umol/L),P<0.05];治疗后OSAHS+CVD组HCY水平仍较OSAHS组高(P<0.05)。结论:1.单纯OSAHS患者血浆HCY浓度较单纯鼾症组高。2.合并心血管疾病的OSAHS患者比单纯OSAHS患者血浆HCY浓度显著升高,hs-CRP亦升高,提示存在炎症反应,推测HCY与OSAHS相关心血管疾病的发生发展有关,且炎症反应可能是其发病机制之一。3.经nCPAP治疗后,单纯OSAHS及OSAHS合并心血管疾病患者血浆HCY浓度均较治疗前有下降,提示有效治疗OSAHS可以预防或减缓心血管方面的损害。更多还原

【Abstract】 ObjectiveThe purpose of this study was to investigate the roles of plasma homocysteine (HCY) in physiopathologic process of obstructive sleep apnea-hypopnea syndrome (OSAHS) with cardiovascular diseases (CVD).MethodsFollowing overnight polysomnographic examination,94 habitual snorers were divided into 3 groups:15 simple snorers,42 simple OSAHS and 37 OSAHS with CVD. In Experiment 1, plasma concentrations of HCY and hs-CRP were measured by immunoturdimetric assay. Levels of Lipid and glucose were measured by Olympus 2700 automatic biochemistry analyzer. Compare difference and correlations of the variables including HCY、hs-CRP、Lipid and glucose among 3 groups. In Experiment2, 30 OSAHS patients and 24 OSAHS with CVD patients accepted nasal continuous positive airway pressure (nCPAP) therapy, the latter continued taking cardiovascular drugs. After 3 month nCPAP therapy, HCY and hs-CRP were measured again.ResultsHCY concentrations gradually increase among simply snorers、OSAHS group and OSAHS+CVD group, and the differences were significant[ separately were(9.42±0.68)umol /L、(12.70±2.45) umol /L、(14.63±2.98)umol/L,F=15.042,P=0.000]. The concentrations of hs-CRP among 3 groups also was different(F=6.855,P=0.002),after tested by S-N-K method, there was significant difference between OSAHS group and OSAHS+CVD group [(1.32±0.61)umol /L VS(2.13±1.87)umol /L, P<0.05]. The concentrations of TC、TG and VLDL also were different in 3 groups, but no entirely significant difference about lipid after S-N-K test. HCY exhibited positively correlations with AHI(r= 0.899、P<0.01)、RIT(r= 0.835、P<0.01)、ODI4(r= 0.760、P<0.01)、TS90%(r= 0.721、P<0.01)、the longest apnea time(r=0.532、P<0.01)、hs-CRP(r=0.542、P<0.01)and negatively correlations with Minspo2(r= -0.749、P<0.01)、Meanspo2(r=-0.673、P<0.01), but no closely correlation with lipid. Stepwise multiple regression analysis showed that AHI and RIT were independently associated with serum homocysteine levels, regression equation was: HCY=8.117+0.085*AHI+0.047*RIT(F=116.231 , P=0.000).After 3 months’nCPAP therapy, HCY concentrations in OSAHS and OSAHS+CVD groups decrease significantly, but it was still higher in OSAHS+CVD group than OSAHS group.Conclusion1. Patients with OSAHS had higher plasma HCY levels than simply snorers.2. Patients with combination of OSAHS and cardiovascular diseases had significant elevated HCY levels in comparison with simply OSAHS subjects, the same to hs-CRP. We hypothesize there were inflammation and hyperhomocysteine may contribute to physiopathologic process of cardiovascular diseases in OSAHS patients by inflammatory response.3. Effective nCPAP therapy can decrease HCY concentrations both in OSAHS and OSAHS+CVD groups, so nCPAP can prevention and relieve cardiovascular damage in OSAHS.更多还原