【作者】 冯惠平；

【导师】 张聪敏；

【作者基本信息】 河北医科大学 ， 内科学， 2002， 硕士

【摘要】 目的：阻塞性睡眠呼吸暂停综合征（ObstructiveSleep Apnea Syndromes，OSAS）是具有潜在危险的常见病，已成为不稳定性心绞痛、心肌梗死、脑中风的独立危险因素，有必要对OSAS患者主要死因—心脑血管栓塞性并发症的发生作进一步研究。OSAS患者心脑血管疾病发病率和死亡率增加的原因仍不明确。已有研究表明血小板活化、凝血激活和继发纤溶亢进在心脑血管动脉粥样硬化中起重要作用。国内外对OSAS患者并发血栓形成的机制及防治方法的研究较少，OSAS患者体内是否也存在血小板活化、凝血激活和继发纤溶亢进，其是否在OSAS患者心脑血管栓塞性并发症高发病率中起作用，国内外尚未对此作系统研究。我们通过检测OSAS患者血浆α-颗粒膜蛋白（GMP-140）、血小板膜糖蛋白Ⅱb／Ⅲa（GPⅡb／Ⅲa）和D-二聚体的变化，了解OSAS患者体内是否也存在血小板活化、凝血激活和继发纤溶亢进及其与低氧血症的关系，进一步从分子生物学角度探讨血小板活化、凝血激活和继发纤溶亢进在OSAS发生发展中的作用及经鼻持续气道正压通气（nCPAP）对其影响。 方法：选择经多导睡眠图（PSG）确诊的OSAS患者58例为实验组，据睡眠呼吸暂停指数（AHI）、最低血氧饱和度（SaO₂min）将OSAS患者分轻度（16例）、中度（17例）、 中文摘要重度组（25例），并设正常对照组 20例，11例重度 OSAS患者接受nCPAP治疗为治疗组，用酶联免疫双抗体夹心法检狈各组血浆 GMP－140、GP 11 b／llla和卜二聚体，＊较各实验组与对照组，治疗组治疗前后的各项指标的差异。 结果：1、轻度 OSAS 患者组血浆 GMP－140、GP 11b、GPllla和 卜h 聚 体分别 为（14．77土2．36）ng／ml。37859．62土1832．52、48461．44土2368．93、（0．29士0．05）mg／I，与 正 常 对 照 组 门4．66士1．72)ng／ml37612．65士565．76、48457．20士1456。sl、（0．28上0．04）mg／1 无明显差异（尸＞0．05）。2、中度 OSAS 患者组血浆GMP－140．GPIb．GPllla和卜二聚体分别为（16．38士2．64）ng／ml、38251．77士860．85、49588．94士955．80 （0．32士0．04）mg／l，均显著高于对照组（HO．05）。3。重度 OSAS 组血浆 GMP－140、GP 11b、GPllla和卜二聚体分别为（18．34士3．27）ng／ml、39505．4S士 1253．60。5091．48士 2399．42、（0．45士0．05）mg八，均显著高于对照组（HO．01）。11例重度OSAS 患者血浆删P－140、GPllb、GPllla 禾 卜h聚体nCPAP 治疗后比 治疗前明显下降 （H 0．01）；4、GMP－140． GP 11b、GPllla禾 ＊二聚体与呼吸暂停低通气指数uHI)呈正相关k分别为 0．5199。0．4761、0．4471、0．7SIS，尸均＜0．001)，与最低 血氧饱和度（Sac；min）呈负相关(r分别为－0．6728、－0．5736。－0．6123、－0．7629，尸均（．001）。 结论：1、中、重度OSAS患者存在血小扳活化、凝血激活和继发纤溶亢进，其在OSAS患者心脑血管栓塞性并发症高发病率中起重要作用，预防并纠正上述病理变化有助 2 中文摘要 于OSAS 患者防止心脑血管栓塞性并发症的发生；2、OSAS 患者血小板活化、凝血激活和继发纤溶亢进与夜间低氧血 症之间存在相关关系，nCPAP治疗可有效逆转上述病理改 变。更多还原

【Abstract】 Objective: Obstractive sleep apnea syndrom(OSAS) is a common health problem with potential risk that has become an independment risk factor for unstable angina,myocardial infarction and brain infraction,so it is necessary to investigate the main death factor-trie high prevalence of cerebrovascular and cardiovascular events in patients with OS AS. The cause of increased cerebrovascular and cardiovascular morbidity and mortality in patients with OSAS is not clear. It have been suggested that plate activation and enhance coagulability, fibrinolytic activa-tion may contribute to the pathogenesis of this condition. Whether plate activation and enhance coagulability, fibrinolytic activa-tion occur and play a role in prevalence of cerebrovascular and cardiovascular events in patients with OSAS is unknown .By measuring changes of Plasma levels of GMP-140, GP lib/III a and D-dimer in patients with OSAS before and after the institution of nasal continuous positive airway pressure (nCPAP), we want to study whether plate activation and enhance coagulability, fibrinolytic activation occur and play a role in prevalence ofcerebrovascular and cardiovascular events in patients with OSAS and the association with hypoxemia, if so, whether therapy with nCPAP alters this effect.Methods: 58 cases diagnosed as OSAS by polysomnography(PSG)were selected as trial group, 20 cases exclude from OSAS by PSG were as control group, and 11 severe OSAS patients were treated by nCPAP and taken as nCPAP therapy group.GMP-140, GPlIb/IIIa and D-dimer were measured by ELISA and compared in these groups.Results: 1. In mild OSAS group, the Plasma levels of GMP-140, GPlIb, GPIIIa and D-dimer were (14.77 ?2.36)ng/ml, 37859.62+1832.52, 48461.44 + 2368.93, (0.29 + 0.05)mg/l respectively. In control group, the values were (14.66+1.72)ng/mK37612.65 + 568.76>48457.20+1486.5K (0.28 + 0.04)mg/l respectively, there were no statistic significant differences. 2. In moderate OSAS group, the value were (16.38 + 2.64)ng/mK 38251.77 +860.85 > 49588.94 + 955.80 ^ (0.32 + 0.04)mg/l respectively, which were significantly higher than that in control group(/><0.05). 3. the Plasma levels of GMP-140, GPII b, GPIIIa and D-dimer were significant higher in severe OSAS group (18.34 + 3.27)ng/mK 39508.48 +1283.60> 50911.48 + 2399.42, (0.45 + 0.05)mg/l than that in control group( PO.01), and in nCPAP therapy group after therapy significantly lower than that before nCPAP therapy(P<0.001). 4. GMP-140, GPIIK GPIIIa and D-dimer were correlated significantly and positively with AHI(r=0.5199, 0.4761, 0.4471, 0.7818, PO.001) and negatively with minimal oxygen saturation(r=-0.6728 -0.5736-0.6123, -0.7629, PO.001).Conclusion: 1. Our findings suggest that activation of platelet and coagulation system combined with fibrinolytic activation occur and may play an important role in the high prevalence of cerebrovascular and cardiovascular events in patients with moderate and severe OSAS. 2. There are a association between activation of platelet and coagulation system combined with fibrinolytic activation in patients with OSAS and hypoxemia, This effect is greatly reduced by nCPAP.更多还原