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TREM-1 和 pentraxin-3 血浆水平及其与儿童阻塞性睡眠呼吸暂停、肥胖和内皮功能的关系。

TREM-1 and pentraxin-3 plasma levels and their association with obstructive sleep apnea, obesity, and endothelial function in children.

机构信息

Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL 60637, USA.

出版信息

Sleep. 2013 Jun 1;36(6):923-31. doi: 10.5665/sleep.2726.

Abstract

BACKGROUND

Obstructive sleep apnea (OSA) is a common health problem in children and increases the risk of cardiovascular disease (CVD). Triggering receptor expressed on myeloid cells-1 (TREM-1) plays an important role in innate immunity and amplifies inflammatory responses. Pentraxin-3 is predominantly released from macrophages and vascular endothelial cells, plays an important role in atherogenesis, and has emerged as a biomarker of CVD risk. Thus, we hypothesized that plasma TREM-1 and pentraxin-3 levels would be elevated in children with OSA.

METHODS

ONE HUNDRED SIX CHILDREN (MEAN AGE: 8.3 ± 1.6 y) were included after they underwent overnight polysomnographic evaluation and a fasting blood sample was drawn the morning after the sleep study. Endothelial function was assessed with a modified hyperemic test after cuff-induced occlusion of the brachial artery. Plasma TREM-1 and pentraxin-3 levels were assayed using commercial enzyme-linked immunosorbent assay kits. Circulating microparticles (MPs) were assessed using flow cytometry after staining with cell-specific antibodies.

RESULTS

Children with OSA had significantly higher TREM-1 and pentraxin-3 levels (versus controls: P < 0.01, P < 0.05, respectively). Plasma TREM-1 was significantly correlated with both body mass index (BMI)-z score and the obstructive apnea-hypopnea index (AHI) in univariate models. Pentraxin-3 levels were inversely correlated with BMI-z score (r = -0.245, P < 0.01), and positively associated with endothelial MPs and platelet MPs (r = 0.230, P < 0.01 and r = 0.302, P < 0.01). Both plasma TREM-1 and pentraxin-3 levels were independently associated with AHI in multivariate models after controlling for age, sex, race, and BMI-z score (P < 0.001 for TREM-1 and P < 0.001 for pentraxin-3). However, no significant associations emerged between TREM-1, pentraxin-3, and endothelial function.

CONCLUSIONS

Plasma TREM-1 and pentraxin-3 levels are elevated in pediatric OSA, and may play a role in modulating the degree of systemic inflammation. The short-term and long-term significance of elevated TREM-1 and pentraxin-3 in OSA-induced end-organ morbidity remains to be defined.

摘要

背景

阻塞性睡眠呼吸暂停(OSA)是儿童常见的健康问题,会增加心血管疾病(CVD)的风险。髓样细胞表达的触发受体-1(TREM-1)在先天免疫中发挥重要作用,并放大炎症反应。血清淀粉样蛋白 P 成分 3 主要由巨噬细胞和血管内皮细胞释放,在动脉粥样硬化形成中发挥重要作用,并已成为 CVD 风险的生物标志物。因此,我们假设 OSA 患儿的血浆 TREM-1 和血清淀粉样蛋白 P 成分 3 水平会升高。

方法

106 名儿童(平均年龄:8.3±1.6 岁)接受了一整夜的多导睡眠图评估,在睡眠研究后的第二天早上抽取了空腹血样。通过袖带引起的肱动脉闭塞后的改良充血试验评估内皮功能。使用商业酶联免疫吸附试验试剂盒测定血浆 TREM-1 和血清淀粉样蛋白 P 成分 3 水平。使用针对细胞特异性抗体的流式细胞术评估循环微颗粒(MPs)。

结果

与对照组相比,OSA 患儿的 TREM-1 和血清淀粉样蛋白 P 成分 3 水平明显升高(P<0.01,P<0.05)。在单变量模型中,血浆 TREM-1 与体重指数(BMI)-z 评分和阻塞性呼吸暂停-低通气指数(AHI)均呈显著相关。血清淀粉样蛋白 P 成分 3 水平与 BMI-z 评分呈负相关(r=-0.245,P<0.01),与内皮 MPs 和血小板 MPs 呈正相关(r=0.230,P<0.01 和 r=0.302,P<0.01)。在控制年龄、性别、种族和 BMI-z 评分后,多变量模型中血浆 TREM-1 和血清淀粉样蛋白 P 成分 3 水平与 AHI 均独立相关(P<0.001 用于 TREM-1,P<0.001 用于血清淀粉样蛋白 P 成分 3)。然而,TREM-1、血清淀粉样蛋白 P 成分 3 与内皮功能之间没有明显的关联。

结论

儿科 OSA 患者的血浆 TREM-1 和血清淀粉样蛋白 P 成分 3 水平升高,可能在调节全身炎症程度方面发挥作用。OSA 引起的终末器官发病率中,TREM-1 和血清淀粉样蛋白 P 成分 3 升高的短期和长期意义仍有待确定。

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