sCD40L与阻塞性睡眠呼吸暂停低通气气合征并并冠心病相关性的研究
发布时间：2018-08-15 17:42
【摘要】：【背景】阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hyponoea syndrome,OSAHS)作为一种常见的睡眠呼吸障碍疾病患病率越来越高,目前国内流行病学调查显示OSAHS的患病率为4.1%,并且越来越多的研究发现OSAHS可并发许多其他疾病,其中冠心病患病率高达20-30%。然而OSAHS并发冠心病(CAD)的机理仍未明确,且仍鲜有炎症介质或因子可以明确并有针对性地证明OSAHS与冠心病的发生和发展密切相关。现有的研究主要主张OSAHS因为存在反复呼吸暂停/低通气,出现低氧血症、高碳酸血症,导致全身炎症反应、自主神经调节紊乱、血管内皮损伤、血流动力学改变、血液纤溶系统功能障碍等,可能是促进动脉粥样硬化形成的机制,但仍未能够全面解释OSASH并发冠心病的机理。目前有关冠心病的观点认为,动脉粥样硬化的发生发展和氧化应激的关系密不可分;冠心病由炎症介质启动,其发生和发展是多种细胞(如单核-巨噬细胞、内皮细胞、平滑肌细胞和血小板等)及其相关因子共同参与、内皮功能失调和炎症反应相互作用导致的一种动态过程。因此,研究OSAHS机体氧化应激情况与并发冠心病的关系将可能揭开OSAHS合并冠心病机制的谜底。有研究发现,sCD40L在冠心病患者血清水平中随着动脉粥样硬化程度增加而升高。sCD40L的高表达与氧自由基(ROS)增多存在正反馈环的关系,sCD40L通过CD40-CD40L通路促进多种与冠心病相关的炎症介质(如ICAM-1、VCAM-1、IL-1、IL-8、TNF-α、ROS、VEGF等)释放,将ROS增多、内皮功能失调和炎症反应紧密相连。总的来说sCD40L被认为是冠心病发生发展危险趋势、严重程度以及预后的重要指标。因此,监测sCD40L在OSAHS患者血清中的变化规律,明确其是否在OSAHS损伤过程中也同样存在其在冠心病病生过程所起的变化,将有助于进一步了解OSAHS并发冠心病的病生机理。 【目的】观察OSAHS患者血清中sCD40L的水平及经鼻持续气道正压通气(nCPAP)治疗后的变化规律,明确其是否在OSAHS损伤过程中也同样存在其在冠心病病生过程所起的变化,进一步了解OSAHS并发冠心病的病生机理。 【方法】111例经过我院睡眠中心诊断或(及)治疗的研究对象行血清sCD40L、CRP、IL-6检测,男性93例,女性18例,年龄47-64岁,平均年龄(55.9±4.86)岁,其中21例AHI5次/h的健康者为正常组,22例AHI5次/h冠心病患者,为冠心病组,35例OSAHS患者,依据AHI分为轻度组(5次/h≤AHI20次/h)、中度组(20次/h≤AHI40次/h)和重度组(AHI≥40次/h),33例OSAHS合并冠心病患者,同样依据AHI分为3个小组。采用多导睡眠仪(PSG)监测所有研究对象睡眠呼吸相关指标。PSG监测当晚禁食12小时,晨起空腹采集静脉血8ml置于普通干燥试管中,常温下离心后,取血清置-80℃低温冰箱保存备测。23例重度OSAHS患者予3个月nCPAP治疗后再次行PSG监测及血清检测。sCD40L、CRP、IL-6水平分别使用对应的特异性ELISA法测定。 【结果】治疗前OSAHS组sCD40L(4.54±0.83)ng/ml、CRP(2.16±0.74)ng/l及IL-6(0.41±0.11)ng/l高于正常组(2.48±0.55)ng/ml、(0.70±0.12)ng/l及(0.24±0.03)ng/l (P0.01),CAD组sCD40L (6.70±0.44)ng/ml、CRP (2.95±0.25)ng/l及IL-6(1.86±0.36)ng/l高于OSAHS组(4.54±0.83)ng/ml、(2.16±0.74)ng/l及(0.41±0.11)ng/l (P0.01),OSAHS+CAD组sCD40L(8.0±1.19)ng/ml、CRP(3.69±1.23)ng/l高于CAD组(6.70±0.44) ng/ml、(2.95±0.25)ng/l (P0.01);治疗前OSAHS组血清sCD40L、CRP、IL-6血清水平与AHI相关系数r分别为0.88、0.61、0.43;OSAHS重度组sCD40L(5.26±0.20)ng/ml高于中度组(4.60±0.37)ng/ml(P0.01),中度组sCD40L高于轻度组(3.43±0.54)ng/ml(P0.01),轻度组sCD40L高于正常组(2.48±0.55)ng/ml(P0.01); OSAHS重度组CRP (2.98±0.22)ng/l高于中度组1.65±0.54)ng/l(P0.01),OSAHS中度组与轻度组间无差异(P0.05),OSAHS中度组与轻度组CRP高于正常组(0.70±0.12)ng/l (P0.01);OSAHS重度组IL-6(0.46±0.13)ng/l高于中度组(0.33±0.12)ng/l(P0.05),OSAHS中度组IL-6与轻度组(0.40±0.11)ng/l)间无差异(P0.05),OSAHS中度组与轻度组IL6高于正常组(0.24±0.03)ng/l(P0.01); OSAHS+CAD重度组sCD40L (9.43±0.58) ng/ml高于中度组(7.69±0. 35)ng/ml、轻度组(6.87±0.55)ng/ml(P0.01),OSAHS+CAD中度组sCD40L高于轻度组及CAD组(6.70±0.44)(P0.01),OSAHS+CAD轻度组与CAD组间无差异(P0.05);OSAHS+CAD重度组CRP(5.19±1.04)ng/l高于OSAHS+CAD中度组(2.96±0.13)ng/l、轻度组(2.92±0.21)ng/l及CAD组(2.95±0.25)ng/l(P0.01),OSAHS+CAD中度组、轻度组及CAD组间CRP无差异(P0.05);OSAHS+CAD重度组IL-6(2.28±0.12)ng/l高于轻度组(1.66±0.35) ng/l、中度组(1.87±0.21)ng/l及CAD组(1.86±0.36)(P0.01),OSAHS+CAD中度组、轻度组及CAD组间IL-6无差异(P0.05);治疗前OSAHS+CAD组血清sCD40L、CRP、IL-6血清水平与AHI相关系数r分别为0.94、0.67、0.51;治疗前sCD40L与CRP、IL-6相关系数为0.72、0.51;治疗前OSAHS组sCD40L与CRP、IL-6相关系数为0.79、0.27;治疗前后重度OSAHS组的IL-6治疗前后没有差异(0.46±0.13)ng/l vs (0.39±0.11)ng/l(P0.05),其余指标治疗后均有改善(P0.01)。 【结论】 1、OSAHS的氧化应激可能触发sCD40L及CD40-CD40L对动脉粥样硬化的促进作用。 2. sCD40L适用于反映OSAHS的病情程度和预测OSAHS并发冠心病的趋势。 3. CRP、IL-6与OSAHS病情严重程度相关性较差,不适用于反映OSAHS的病情程度和预测OSAHS并发冠心病的趋势。 4. nCPAP不仅能改善OSAHS患者的睡眠呼吸功能,同时可能有利于减少OSAHS并发冠心病的风险、缓解OSAHS合并冠心病患者动脉粥样硬化进程。
[Abstract]:[Background] The prevalence of obstructive sleep apnea hyponoea syndrome (OSAHS) as a common sleep apnea disorder is becoming higher and higher. At present, the prevalence of OSAHS is 4.1% in domestic epidemiological survey, and more and more studies have found that OSAHS can be complicated with many other diseases. However, the mechanism of OSAHS complicated with coronary heart disease (CAD) is still unclear, and few inflammatory mediators or factors can clearly and specifically prove that OSAHS is closely related to the occurrence and development of coronary heart disease. Hypercapnia, leading to systemic inflammation, autonomic nervous dysregulation, vascular endothelial damage, hemodynamic changes, dysfunction of the blood fibrinolytic system, may be the mechanism of atherosclerosis, but still can not fully explain the mechanism of OSASH with coronary heart disease. The development of sclerosis is closely related to oxidative stress. Coronary heart disease is initiated by inflammatory mediators. The occurrence and development of coronary heart disease is a dynamic process caused by the interaction between endothelial dysfunction and inflammation, which is caused by the co-participation of a variety of cells (such as monocytes-macrophages, endothelial cells, smooth muscle cells and platelets) and related factors. Therefore, the study of the relationship between oxidative stress and coronary heart disease in OSAHS may reveal the mystery of the mechanism of OSAHS complicated with coronary heart disease. Over CD40-CD40L pathway promotes the release of many inflammatory mediators (such as ICAM-1, VCAM-1, IL-1, IL-8, TNF-alpha, ROS, and VEGF) associated with increased ROS, endothelial dysfunction and inflammation. Overall, sCD40L is considered to be an important indicator of risk trends, severity and prognosis of coronary heart disease. The changes of L in serum of patients with OSAHS and the changes of L in coronary heart disease during OSAHS injury will be helpful to understand the pathogenesis of OSAHS complicated with coronary heart disease.
[Objective] To observe the changes of serum sCD40L levels in patients with OSAHS and after nasal continuous positive airway pressure (nCPAP) treatment, and to determine whether there are changes of sCD40L levels in the process of coronary heart disease (CHD) in patients with OSAHS.
[Methods] The serum sCD40L, CRP and IL-6 levels were detected in 111 subjects diagnosed or treated by sleep center in our hospital. 93 males and 18 females aged 47-64 with an average age of (55.9.86). 21 healthy subjects with AHI 5 times / h were normal group, 22 patients with AHI 5 times / h coronary heart disease were coronary heart disease group, 35 patients with OSAHS were divided into two groups according to AHI. The mild group (5 times / h < AHI 20 times / h), the moderate group (20 times / h < AHI 40 times / h) and the severe group (AHI < 40 times / h), 33 patients with OSAHS complicated with coronary heart disease were divided into three groups according to AHI. Sleep breathing related indexes were monitored by polysomnography (PSG). PSG monitored fasting for 12 hours on the same night, and 8 ml of venous blood was collected on an empty stomach in the morning. After centrifugation at room temperature, 23 patients with severe OSAHS were treated with nCPAP for 3 months. The levels of sCD40L, CRP and IL-6 were determined by specific ELISA.
[Results] Before treatment, the sCD40L (4.54 (+ 0.83) ng/ml, CRP (2.16 (+ 0.74) ng/ml, CRP (2.16 (+ 0.74) ng/ml and IL-6 (0.41 (+ 0.11) ng/ml in OSAHS group were significantly higher than those in normal group (2.48 (+ 0.55) ng/ml, (0.48 [(0.55)ng/ml, (0.70 [(0.70 [0.12) ng/l, (0.70 [(0.70 [0.12) ng/l, (0.24 [0.03) ng/l, (P 0.01). sCD40L (6.70 ((6.70 / l was higher than (4.54 + 0.83) ng / ml, (2.16 + 0.74) ng / L and (0. (P 0.01). The sCD40L (8.0 (+ 1.19) ng/ml, CRP (3.69 (1.23) ng/ml) was significantly higher in OSAHS + CAD group than in CAD group (6.70 (+ 0.44) ng/ml, (2.95 (+ 0.25) ng/l (P 0.01); the correlation coer of sersCD40L, CRP, IL-6 and IL-6 levels with AHI were 0.88, 0.88, 0.61, 0.61, 0.43 in OSAHS + CAD group, 0.88, 0.88, 0.88, 0.61, 0.43 in OSAHS severe group, sCD40L (5.26 (+ 5.26 [0.20.20.20.20 Group A (4.60 + 0.37) ng/ml (P 0. The sCD40L in moderate group was higher than that in mild group (3.43.54) ng/ml (P 0.01), the sCD40L in mild group was higher than that in normal group (2.48.55) ng/ml (P 0.01), the CRP (2.98.22) ng/l in severe OSAHS group was higher than that in moderate group (1.65.54) ng/l (P 0.01), and the CRP (P 0.05) in moderate OSAHS group and mild OSAHS group was higher than that in normal group (0.70.12). There was no significant difference (P 0.05) between IL-6 in OSAHS moderate group and mild group (0.40 [0.40 [0.11) ng/l (P 0.05). IL-6 in OSAHS modemoderate group was higher than that in normal group (0.24 [0.03] ng/l (P 0.01); IL-6 in OSAHS modemoderate group and milOSAHS moderate group was higher than that in normal group (0.24 [(0.24 [0.03) ng/l (P 0.01); sCD40L (9.43 [9.43 [0.43 [0.58] 0.58) sCD40L (9.43 [0.43 [0.58] 0.58) was higher than that in OSAHS modemodeng / ml, mild group( There was no significant difference between OSAHS + CAD milgroup and CAD group (P 0.01), OSAHS + CAD modegroup (OSAHS + CAD group) and OSCD40L was significantly higher than milOSAHS + CAD milgroup and CAD group (6.70 0.44 (P 0.01), OSAHS + CAD milOSAHS + CAD group and CAD group (P 0.05), OSAHS + CAD severe OSAHS + CAD group CRP (5.19 1.19 1.04) ng/l was significantly higher than OSOSOSAHS + OSAHS + CAD modeOSAHS + CAD modeOSAHS + CAD group (2.96 0.96 0.96 0.13) ng/l, 2.92 (2.92 0.92 0.92 0.21) ng / 0.21) ng OSAHS + CAD moderate group, mild There was no significant difference in CRP between the moderate group and CAD group (P 0.05); the serum levels of IL-6 (2.28.12) ng/l in OSAHS+CAD group were higher than those in mild group (1.66.35) ng/l, moderate group (1.87.21) ng/l and CAD group (1.86.36) (P 0.01), OSAHS+CAD moderate group, mild group and CAD group (P 0.05). The correlation coefficients of sCD40L and CRP, IL-6 were 0.72 and 0.51 before treatment, 0.79 and 0.27 between sCD40L and CRP, 0.67 and 0.51 before treatment in OSAHS group, and 0.46 (+ 0.13) ng/l vs 0.39 (+ 0.11) ng/l (P 0.05) in severe OSAHS group before and after treatment, while the other indexes improved after treatment (P 0.01).
[Conclusion]
1, oxidative stress of OSAHS may trigger sCD40L and CD40-CD40L to promote atherosclerosis.
2. sCD40L is suitable for reflecting the severity of OSAHS and predicting the trend of OSAHS complicated with coronary heart disease.
3. CRP, IL-6 and severity of OSAHS are poorly correlated. They are not suitable for reflecting the severity of OSAHS and predicting the trend of coronary heart disease in OSAHS.
4. nCPAP can not only improve the sleep respiratory function of OSAHS patients, but also reduce the risk of coronary heart disease and alleviate the atherosclerosis process of OSAHS patients with coronary heart disease.
【学位授予单位】：广州医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R766;R541.4
本文编号：2184941
[Abstract]:[Background] The prevalence of obstructive sleep apnea hyponoea syndrome (OSAHS) as a common sleep apnea disorder is becoming higher and higher. At present, the prevalence of OSAHS is 4.1% in domestic epidemiological survey, and more and more studies have found that OSAHS can be complicated with many other diseases. However, the mechanism of OSAHS complicated with coronary heart disease (CAD) is still unclear, and few inflammatory mediators or factors can clearly and specifically prove that OSAHS is closely related to the occurrence and development of coronary heart disease. Hypercapnia, leading to systemic inflammation, autonomic nervous dysregulation, vascular endothelial damage, hemodynamic changes, dysfunction of the blood fibrinolytic system, may be the mechanism of atherosclerosis, but still can not fully explain the mechanism of OSASH with coronary heart disease. The development of sclerosis is closely related to oxidative stress. Coronary heart disease is initiated by inflammatory mediators. The occurrence and development of coronary heart disease is a dynamic process caused by the interaction between endothelial dysfunction and inflammation, which is caused by the co-participation of a variety of cells (such as monocytes-macrophages, endothelial cells, smooth muscle cells and platelets) and related factors. Therefore, the study of the relationship between oxidative stress and coronary heart disease in OSAHS may reveal the mystery of the mechanism of OSAHS complicated with coronary heart disease. Over CD40-CD40L pathway promotes the release of many inflammatory mediators (such as ICAM-1, VCAM-1, IL-1, IL-8, TNF-alpha, ROS, and VEGF) associated with increased ROS, endothelial dysfunction and inflammation. Overall, sCD40L is considered to be an important indicator of risk trends, severity and prognosis of coronary heart disease. The changes of L in serum of patients with OSAHS and the changes of L in coronary heart disease during OSAHS injury will be helpful to understand the pathogenesis of OSAHS complicated with coronary heart disease.
[Objective] To observe the changes of serum sCD40L levels in patients with OSAHS and after nasal continuous positive airway pressure (nCPAP) treatment, and to determine whether there are changes of sCD40L levels in the process of coronary heart disease (CHD) in patients with OSAHS.
[Methods] The serum sCD40L, CRP and IL-6 levels were detected in 111 subjects diagnosed or treated by sleep center in our hospital. 93 males and 18 females aged 47-64 with an average age of (55.9.86). 21 healthy subjects with AHI 5 times / h were normal group, 22 patients with AHI 5 times / h coronary heart disease were coronary heart disease group, 35 patients with OSAHS were divided into two groups according to AHI. The mild group (5 times / h < AHI 20 times / h), the moderate group (20 times / h < AHI 40 times / h) and the severe group (AHI < 40 times / h), 33 patients with OSAHS complicated with coronary heart disease were divided into three groups according to AHI. Sleep breathing related indexes were monitored by polysomnography (PSG). PSG monitored fasting for 12 hours on the same night, and 8 ml of venous blood was collected on an empty stomach in the morning. After centrifugation at room temperature, 23 patients with severe OSAHS were treated with nCPAP for 3 months. The levels of sCD40L, CRP and IL-6 were determined by specific ELISA.
[Results] Before treatment, the sCD40L (4.54 (+ 0.83) ng/ml, CRP (2.16 (+ 0.74) ng/ml, CRP (2.16 (+ 0.74) ng/ml and IL-6 (0.41 (+ 0.11) ng/ml in OSAHS group were significantly higher than those in normal group (2.48 (+ 0.55) ng/ml, (0.48 [(0.55)ng/ml, (0.70 [(0.70 [0.12) ng/l, (0.70 [(0.70 [0.12) ng/l, (0.24 [0.03) ng/l, (P 0.01). sCD40L (6.70 ((6.70 / l was higher than (4.54 + 0.83) ng / ml, (2.16 + 0.74) ng / L and (0. (P 0.01). The sCD40L (8.0 (+ 1.19) ng/ml, CRP (3.69 (1.23) ng/ml) was significantly higher in OSAHS + CAD group than in CAD group (6.70 (+ 0.44) ng/ml, (2.95 (+ 0.25) ng/l (P 0.01); the correlation coer of sersCD40L, CRP, IL-6 and IL-6 levels with AHI were 0.88, 0.88, 0.61, 0.61, 0.43 in OSAHS + CAD group, 0.88, 0.88, 0.88, 0.61, 0.43 in OSAHS severe group, sCD40L (5.26 (+ 5.26 [0.20.20.20.20 Group A (4.60 + 0.37) ng/ml (P 0. The sCD40L in moderate group was higher than that in mild group (3.43.54) ng/ml (P 0.01), the sCD40L in mild group was higher than that in normal group (2.48.55) ng/ml (P 0.01), the CRP (2.98.22) ng/l in severe OSAHS group was higher than that in moderate group (1.65.54) ng/l (P 0.01), and the CRP (P 0.05) in moderate OSAHS group and mild OSAHS group was higher than that in normal group (0.70.12). There was no significant difference (P 0.05) between IL-6 in OSAHS moderate group and mild group (0.40 [0.40 [0.11) ng/l (P 0.05). IL-6 in OSAHS modemoderate group was higher than that in normal group (0.24 [0.03] ng/l (P 0.01); IL-6 in OSAHS modemoderate group and milOSAHS moderate group was higher than that in normal group (0.24 [(0.24 [0.03) ng/l (P 0.01); sCD40L (9.43 [9.43 [0.43 [0.58] 0.58) sCD40L (9.43 [0.43 [0.58] 0.58) was higher than that in OSAHS modemodeng / ml, mild group( There was no significant difference between OSAHS + CAD milgroup and CAD group (P 0.01), OSAHS + CAD modegroup (OSAHS + CAD group) and OSCD40L was significantly higher than milOSAHS + CAD milgroup and CAD group (6.70 0.44 (P 0.01), OSAHS + CAD milOSAHS + CAD group and CAD group (P 0.05), OSAHS + CAD severe OSAHS + CAD group CRP (5.19 1.19 1.04) ng/l was significantly higher than OSOSOSAHS + OSAHS + CAD modeOSAHS + CAD modeOSAHS + CAD group (2.96 0.96 0.96 0.13) ng/l, 2.92 (2.92 0.92 0.92 0.21) ng / 0.21) ng OSAHS + CAD moderate group, mild There was no significant difference in CRP between the moderate group and CAD group (P 0.05); the serum levels of IL-6 (2.28.12) ng/l in OSAHS+CAD group were higher than those in mild group (1.66.35) ng/l, moderate group (1.87.21) ng/l and CAD group (1.86.36) (P 0.01), OSAHS+CAD moderate group, mild group and CAD group (P 0.05). The correlation coefficients of sCD40L and CRP, IL-6 were 0.72 and 0.51 before treatment, 0.79 and 0.27 between sCD40L and CRP, 0.67 and 0.51 before treatment in OSAHS group, and 0.46 (+ 0.13) ng/l vs 0.39 (+ 0.11) ng/l (P 0.05) in severe OSAHS group before and after treatment, while the other indexes improved after treatment (P 0.01).
[Conclusion]
1, oxidative stress of OSAHS may trigger sCD40L and CD40-CD40L to promote atherosclerosis.
2. sCD40L is suitable for reflecting the severity of OSAHS and predicting the trend of OSAHS complicated with coronary heart disease.
3. CRP, IL-6 and severity of OSAHS are poorly correlated. They are not suitable for reflecting the severity of OSAHS and predicting the trend of coronary heart disease in OSAHS.
4. nCPAP can not only improve the sleep respiratory function of OSAHS patients, but also reduce the risk of coronary heart disease and alleviate the atherosclerosis process of OSAHS patients with coronary heart disease.
【学位授予单位】：广州医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R766;R541.4
【参考文献】
相关期刊论文 前1条
1 中华医学会呼吸病学分会睡眠呼吸疾病学组;阻塞性睡眠呼吸暂停低通气综合征诊治指南(草案)[J];中华内科杂志;2003年08期
，本文编号：2184941
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