阻塞性睡眠呼吸暂停患者血白三烯B4和动脉粥样硬化关系的研究

Study of leukotriene B4 and early mediators of atherosclerosis in obstructive sleep apnea patients

关键词:  阻塞性睡眠呼吸暂停  白三烯B4  动脉粥样硬化

Key words:  obstructive sleep apnoea  leukotriene B4  atherosclerosis

摘要:

目的　研究不同缺氧程度阻塞性睡眠呼吸暂停(OSA)患者血清白三烯B4(leukotriene B4，LTB4)水平和动脉粥样硬化的关系，探讨OSA患者发生心血管疾病的可能机制。方法 　选取非肥胖无心血管疾病的OSA患者40例和正常对照组20例，按照平均血氧饱和度分为轻度缺氧OSA组（SpO₂>94%）（18例）和中重度缺氧OSA组（SpO₂≤94%）（22例），检测颈动脉内膜中层厚度（IMT）和颈动脉直径，各组均于睡眠监测后采空腹静脉血，应用酶联免疫吸附法(ELISA)检测血清LTB4水平，评估LTB4和不同缺氧程度OSA以及早期动脉粥样硬化的关系，及OSA患者经过自动持续气道正压通气（Auto-CPAP）或持续气道正压通气（CPAP）治疗后LTB4的变化。结果　中重度缺氧OSA组较轻度缺氧OSA组、对照组LTB4水平升高，差异有统计学意义(P<0.05)。LTB4值与夜间最低和平均血氧饱和度(SpO₂)、氧减指数(ODI)、血氧饱和度＜0.9时间占睡眠时间百分比(SLT90％)、睡眠呼吸暂停低通气指数(AHI)均相关(P<0.05)，多元回归分析显示平均SpO₂是LTB4水平最强的独立预测因素（P=0.0005，P<0.05）。在中重度缺氧OSA组中，LTB4和颈动脉直径相关(P<0.05)，然而在各组中颈动脉IMT均与LTB4无相关(P=0.77)。中重度缺氧OSA组中15例患者经过3个月的Auto-CPAP或CPAP治疗，LTB4水平下降，差异有统计学意义(P<0.05)。结论　在OSA患者中LTB4产生增加，与氧减饱和度严重性相关，LTB4促进中重度缺氧OSA患者的血管重塑。

Abstract:

Objective To investigate the relationship between serum leukotriene B4 (LTB4) level and atherosclerosis in obstructive sleep apnea (OSA) patients with different severity of oxygen desaturation，and to explore the possible mechanisms of cardiovascular diseases in OSA patients．Methods Study objects included 40 non-obese OSA patients without a cardiovascular history and 20 healthy volunteers. The mean SpO₂ was used to divide the OSA patients into mild hypoxic OSA group (SpO₂>94%) and moderate-to-severe hypoxic OSA group (SpO2≤94%). An overnight sleep study was followed by first-morning blood sampling, Carotid intima-media thickness (IMT) and lumina diameter measurement. Serum LTB4 levels were measured by ELISA. The relationships between serum LTB4 level and degree of OSA hypoxia as well as early atherosclerosis markers were evaluated. The effect of Auto continuous positive airway pressure (Auto-CPAP) or continuous positive airway pressure (CPAP) on LTB4 production was also studied. Results The serum LTB4 level in moderate to severe hypoxic OSA group was higher than that in mild hypoxic OSA group and control group (P<0.05)．The serum LTB4 level was correlated with mean and minimal arterial oxygen saturation (SpO₂), ODI, SLT90％and AHI (all P<0.05)．Multiple regression analysis revealed that the mean arterial oxygen saturation (SpO₂) was an independent risk factor to influence the level of serum LTB4 in patients with OSA（P<0.05）.LTB4 production was correlated with luminal diameter in patients with a mean SpO₂ ≤94% but not with IMT. Auto-CPAP or CPAP significantly reduced LTB4 production in the fifteen moderate-to-severe hypoxic OSA patients. Conclusions Leukotriene B4 production is increased in OSA patients in relation to oxygen desaturation. Leukotriene B4 could promote early vascular remodelling in moderate-to-severe hypoxic OSA patients.