【摘要】：【背景】阻塞性睡眠呼吸暫停低通氣綜合征(obstructive sleep apnea hyponoea syndrome,OSAHS)作為一種常見的睡眠呼吸障礙疾病患病率越來越高,目前國內(nèi)流行病學(xué)調(diào)查顯示OSAHS的患病率為4.1%,并且越來越多的研究發(fā)現(xiàn)OSAHS可并發(fā)許多其他疾病,其中冠心病患病率高達(dá)20-30%。然而OSAHS并發(fā)冠心病(CAD)的機(jī)理仍未明確,且仍鮮有炎癥介質(zhì)或因子可以明確并有針對性地證明OSAHS與冠心病的發(fā)生和發(fā)展密切相關(guān)。現(xiàn)有的研究主要主張OSAHS因?yàn)榇嬖诜磸?fù)呼吸暫停/低通氣,出現(xiàn)低氧血癥、高碳酸血癥,導(dǎo)致全身炎癥反應(yīng)、自主神經(jīng)調(diào)節(jié)紊亂、血管內(nèi)皮損傷、血流動(dòng)力學(xué)改變、血液纖溶系統(tǒng)功能障礙等,可能是促進(jìn)動(dòng)脈粥樣硬化形成的機(jī)制,但仍未能夠全面解釋OSASH并發(fā)冠心病的機(jī)理。目前有關(guān)冠心病的觀點(diǎn)認(rèn)為,動(dòng)脈粥樣硬化的發(fā)生發(fā)展和氧化應(yīng)激的關(guān)系密不可分;冠心病由炎癥介質(zhì)啟動(dòng),其發(fā)生和發(fā)展是多種細(xì)胞(如單核-巨噬細(xì)胞、內(nèi)皮細(xì)胞、平滑肌細(xì)胞和血小板等)及其相關(guān)因子共同參與、內(nèi)皮功能失調(diào)和炎癥反應(yīng)相互作用導(dǎo)致的一種動(dòng)態(tài)過程。因此,研究OSAHS機(jī)體氧化應(yīng)激情況與并發(fā)冠心病的關(guān)系將可能揭開OSAHS合并冠心病機(jī)制的謎底。有研究發(fā)現(xiàn),sCD40L在冠心病患者血清水平中隨著動(dòng)脈粥樣硬化程度增加而升高。sCD40L的高表達(dá)與氧自由基(ROS)增多存在正反饋環(huán)的關(guān)系,sCD40L通過CD40-CD40L通路促進(jìn)多種與冠心病相關(guān)的炎癥介質(zhì)(如ICAM-1、VCAM-1、IL-1、IL-8、TNF-α、ROS、VEGF等)釋放,將ROS增多、內(nèi)皮功能失調(diào)和炎癥反應(yīng)緊密相連。總的來說sCD40L被認(rèn)為是冠心病發(fā)生發(fā)展危險(xiǎn)趨勢、嚴(yán)重程度以及預(yù)后的重要指標(biāo)。因此,監(jiān)測sCD40L在OSAHS患者血清中的變化規(guī)律,明確其是否在OSAHS損傷過程中也同樣存在其在冠心病病生過程所起的變化,將有助于進(jìn)一步了解OSAHS并發(fā)冠心病的病生機(jī)理。 【目的】觀察OSAHS患者血清中sCD40L的水平及經(jīng)鼻持續(xù)氣道正壓通氣(nCPAP)治療后的變化規(guī)律,明確其是否在OSAHS損傷過程中也同樣存在其在冠心病病生過程所起的變化,進(jìn)一步了解OSAHS并發(fā)冠心病的病生機(jī)理。 【方法】111例經(jīng)過我院睡眠中心診斷或(及)治療的研究對象行血清sCD40L、CRP、IL-6檢測,男性93例,女性18例,年齡47-64歲,平均年齡(55.9±4.86)歲,其中21例AHI5次/h的健康者為正常組,22例AHI5次/h冠心病患者,為冠心病組,35例OSAHS患者,依據(jù)AHI分為輕度組(5次/h≤AHI20次/h)、中度組(20次/h≤AHI40次/h)和重度組(AHI≥40次/h),33例OSAHS合并冠心病患者,同樣依據(jù)AHI分為3個(gè)小組。采用多導(dǎo)睡眠儀(PSG)監(jiān)測所有研究對象睡眠呼吸相關(guān)指標(biāo)。PSG監(jiān)測當(dāng)晚禁食12小時(shí),晨起空腹采集靜脈血8ml置于普通干燥試管中,常溫下離心后,取血清置-80℃低溫冰箱保存?zhèn)錅y。23例重度OSAHS患者予3個(gè)月nCPAP治療后再次行PSG監(jiān)測及血清檢測。sCD40L、CRP、IL-6水平分別使用對應(yīng)的特異性ELISA法測定。 【結(jié)果】治療前OSAHS組sCD40L(4.54±0.83)ng/ml、CRP(2.16±0.74)ng/l及IL-6(0.41±0.11)ng/l高于正常組(2.48±0.55)ng/ml、(0.70±0.12)ng/l及(0.24±0.03)ng/l (P0.01),CAD組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組(4.54±0.83)ng/ml、(2.16±0.74)ng/l及(0.41±0.11)ng/l (P0.01),OSAHS+CAD組sCD40L(8.0±1.19)ng/ml、CRP(3.69±1.23)ng/l高于CAD組(6.70±0.44) ng/ml、(2.95±0.25)ng/l (P0.01);治療前OSAHS組血清sCD40L、CRP、IL-6血清水平與AHI相關(guān)系數(shù)r分別為0.88、0.61、0.43;OSAHS重度組sCD40L(5.26±0.20)ng/ml高于中度組(4.60±0.37)ng/ml(P0.01),中度組sCD40L高于輕度組(3.43±0.54)ng/ml(P0.01),輕度組sCD40L高于正常組(2.48±0.55)ng/ml(P0.01); OSAHS重度組CRP (2.98±0.22)ng/l高于中度組1.65±0.54)ng/l(P0.01),OSAHS中度組與輕度組間無差異(P0.05),OSAHS中度組與輕度組CRP高于正常組(0.70±0.12)ng/l (P0.01);OSAHS重度組IL-6(0.46±0.13)ng/l高于中度組(0.33±0.12)ng/l(P0.05),OSAHS中度組IL-6與輕度組(0.40±0.11)ng/l)間無差異(P0.05),OSAHS中度組與輕度組IL6高于正常組(0.24±0.03)ng/l(P0.01); OSAHS+CAD重度組sCD40L (9.43±0.58) ng/ml高于中度組(7.69±0. 35)ng/ml、輕度組(6.87±0.55)ng/ml(P0.01),OSAHS+CAD中度組sCD40L高于輕度組及CAD組(6.70±0.44)(P0.01),OSAHS+CAD輕度組與CAD組間無差異(P0.05);OSAHS+CAD重度組CRP(5.19±1.04)ng/l高于OSAHS+CAD中度組(2.96±0.13)ng/l、輕度組(2.92±0.21)ng/l及CAD組(2.95±0.25)ng/l(P0.01),OSAHS+CAD中度組、輕度組及CAD組間CRP無差異(P0.05);OSAHS+CAD重度組IL-6(2.28±0.12)ng/l高于輕度組(1.66±0.35) ng/l、中度組(1.87±0.21)ng/l及CAD組(1.86±0.36)(P0.01),OSAHS+CAD中度組、輕度組及CAD組間IL-6無差異(P0.05);治療前OSAHS+CAD組血清sCD40L、CRP、IL-6血清水平與AHI相關(guān)系數(shù)r分別為0.94、0.67、0.51;治療前sCD40L與CRP、IL-6相關(guān)系數(shù)為0.72、0.51;治療前OSAHS組sCD40L與CRP、IL-6相關(guān)系數(shù)為0.79、0.27;治療前后重度OSAHS組的IL-6治療前后沒有差異(0.46±0.13)ng/l vs (0.39±0.11)ng/l(P0.05),其余指標(biāo)治療后均有改善(P0.01)。 【結(jié)論】 1、OSAHS的氧化應(yīng)激可能觸發(fā)sCD40L及CD40-CD40L對動(dòng)脈粥樣硬化的促進(jìn)作用。 2. sCD40L適用于反映OSAHS的病情程度和預(yù)測OSAHS并發(fā)冠心病的趨勢。 3. CRP、IL-6與OSAHS病情嚴(yán)重程度相關(guān)性較差,不適用于反映OSAHS的病情程度和預(yù)測OSAHS并發(fā)冠心病的趨勢。 4. nCPAP不僅能改善OSAHS患者的睡眠呼吸功能,同時(shí)可能有利于減少OSAHS并發(fā)冠心病的風(fēng)險(xiǎn)、緩解OSAHS合并冠心病患者動(dòng)脈粥樣硬化進(jìn)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.
【學(xué)位授予單位】：廣州醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R766;R541.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 中華醫(yī)學(xué)會(huì)呼吸病學(xué)分會(huì)睡眠呼吸疾病學(xué)組;阻塞性睡眠呼吸暫停低通氣綜合征診治指南(草案)[J];中華內(nèi)科雜志;2003年08期

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