终末糖基化终产物在心衰合并睡眠呼吸暂停综合征中的影响

The influence of advanced glycation endproducts on heart failure with sleep apnea syndrome

目的高迁移率族蛋白1(High-mobility group box-1,HMGB1)是终末糖基化终产物受体(Receptor for advanced glycation endproducts,RAGE)的配体。HMGB1通过与RAGE相互作用对心功能不全的影响已被证实。睡眠呼吸暂停综合征(Sleep apnea syndrome,SAS)以慢性间歇性缺氧引起炎症反应,加剧心血管疾病的发生发展。研究旨在评估心力衰竭(Heart failure,HF)合并SAS患者血清HMGB1水平以及SAS对心力衰竭的影响。方法我们共检测了165(男性141例,年龄62.88±10.77)例患者的血清HMGB1、高敏C反应蛋白(High-sensitivity C-reactive protein,hs CRP)和前脑钠素氨基末端肽(N-terminal pro-brain natriuretic peptide,NT-pro BNP),同时采用经胸超声心动图评估患者的左室结构和功能。其中,68例诊断为心力衰竭合并SAS,另外70例诊断为单纯性心力衰竭,其余27例作为对照。结果心衰患者血清HMGB1、hs CRP和NT-pro BNP水平及纽约心脏学会(New York Heart Association,NYHA)功能分级明显较对照组高(P<0.001),心衰患者的左室收缩末和舒张末内径较对照组增加(P<0.001),而射血分数比对照组明显减少(P<0.001);此外,心力衰竭合并SAS患者的血清HMGB1、hs-CRP水平较单纯性心力衰竭患者升高(P=0.011;P=0.017);心衰患者血清HMGB1水平与NT-pro BNP和hs CRP水平呈正相关(分别为γ=0.622;γ=0.682)。多因素回归分析显示HMGB1是心力衰竭发病的独立危险因素。结论血清HMGB1、hsCRP、NT-pro BNP水平在心力衰竭时升高,心力衰竭合并SAS时HMGB1升高尤为显著,且HMGB1是心力衰竭发病的独立危险因素。因此,HMGB1是SAS影响心力衰竭发病及进展的关键因素。

Objective High-mobility group box-1（HMGB1） is a ligand for the receptor of advanced glycation endproducts（RAGE）. It has been confirmed that the interaction of HMGB1 with RAGE influence cardiac dysfunction. Sleep apnea syndrome（SAS） induces inflammation by the pathophysiology of chronic intermittent hypoxia,it exacerbates the incidence and development of cardiovascular disease. The study aimed to assess the serum levels of HMGB1 in patients with heart failure（HF） and SAS,while to explore the association between SAS and heart failure. Methods We assayed serum levels of HMGB1,high-sensitivity C-reactive protein（hs CRP） and N-terminal pro-brain natriuretic peptide（NT-pro BNP）,and assessed left ventricular structure and function in 68 SAS and 70 non-SAS patients compined with chronic HF. Of the total 27 normal subjects served as normal controls.Results the levels of Serum HMGB1,hs CRP and NT-pro BNP,left ventricular end-diastolic and end-systolic diameters,and New York Heart Association functional（NYHA） class were higher and,in contrast,left ventricular ejection fraction lower in HF patients than those in subjects without HF（for all;P〈0.001）,while higher levels of HMGB1 and hs CRP in SAS HF vs. non-SAS HF patients（P=0.011 and P=0.017,respectively）. For HF patients-with or without SAS-HMGB1 levels correlated positively with NT-pro BNP and hs CRP values（γ=0.622,γ=0.682,all P〈0.001）. Multivariable regression analysis revealed that HMGB1 was the independent risk factor in HF patients with or without SAS. Conclusion The levels of serum HMGB1,hs-CRP and NT-pro BNP were increased in heart failure,and HMGB1 was significantly elevated in heart failure patients with SAS,and HMGB1 was an independent risk factor for heart failure. Therefore,HMGB1 is the key factor that affects the incidence and progression of heart failure in SAS.