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暴露于间歇性低氧的肺气肿大鼠的系统性和内皮炎症及内皮祖细胞水平

Systematic and endothelial inflammation and endothelial progenitor cell levels in emphysematous rats exposed to intermittent hypoxia.

作者信息

Yang Qing-chan, Sun Xin, Wang Yong-mei, Wu Qi, Feng Jing, Chen Bao-yuan

机构信息

Tianjin Haihe Hospital, Tianjin, China.

Respiratory Department, Tianjin Medical University General Hospital, Tianjin, China. Neuropharmacology Section, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.

出版信息

Respir Care. 2015 Feb;60(2):279-89. doi: 10.4187/respcare.03492. Epub 2015 Jan 13.

Abstract

BACKGROUND

This study aimed to develop an overlap syndrome rat model with intermittent hypoxia (IH) exposure as seen in obstructive sleep apnea, on a base of preexisting emphysema caused by 16 wk of smoke exposure to determine whether IH and emphysema existing simultaneously play overlapped roles on systematic/endothelial inflammation and endothelial damage.

METHODS

Sixty male Wistar rats were divided into 4 groups of 15 each, labeled according to exposure conditions as control, IH, emphysema, and overlap groups. In these animals, electroencephalogram monitoring and preliminary experiments to obtain arterial blood gas values were performed. Serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6, TNF-α and IL-6 concentrations in the culture medium, Ras homology A mRNA expression levels of endothelial cells from right common carotid artery, and ratio of carotid intima-media thickness of whole thickness of vascular wall expressed in percent (C-IMT) (%) values were evaluated. Subsequently, circulating endothelial progenitor cells (EPCs) within rat peripheral blood and bone marrow were measured with flow cytometry.

RESULTS

The serum and endothelial concentrations of TNF-α and IL-6 and the levels of endothelial Ras homology A mRNA have statistically significant results described as overlap>emphysema>IH>control. The levels of EPCs in rat peripheral blood and bone marrow have statistically significant results described as overlap>IH>emphysema>control. C-IMT (%) values from right common carotid artery are the highest in the overlap group and the lowest in the control group. There is no statistical difference when comparing the IH and the emphysema groups.

CONCLUSIONS

Regardless of whether IH and emphysema exposure are mechanistically synergistic, this overlap elicits a more severe systematic/endothelial inflammation and endothelial damage; meanwhile, a robust mobilization of EPCs is demonstrated, which is not to mean a robust adherent and repairing capability.

摘要

背景

本研究旨在建立一种阻塞性睡眠呼吸暂停中所见的间歇性低氧(IH)暴露的重叠综合征大鼠模型,该模型基于16周烟雾暴露导致的预先存在的肺气肿,以确定IH和肺气肿同时存在是否对全身/内皮炎症和内皮损伤起重叠作用。

方法

60只雄性Wistar大鼠分为4组,每组15只,根据暴露条件标记为对照组、IH组、肺气肿组和重叠组。对这些动物进行脑电图监测和获取动脉血气值的初步实验。评估血清肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6浓度、培养基中TNF-α和IL-6浓度、右颈总动脉内皮细胞的Ras同源A mRNA表达水平以及以血管壁全厚度百分比表示的颈动脉内膜中层厚度比值(C-IMT)(%)值。随后,用流式细胞术测量大鼠外周血和骨髓中的循环内皮祖细胞(EPC)。

结果

TNF-α和IL-6的血清及内皮浓度以及内皮Ras同源A mRNA水平具有统计学显著结果,描述为重叠组>肺气肿组>IH组>对照组。大鼠外周血和骨髓中的EPC水平具有统计学显著结果,描述为重叠组>IH组>肺气肿组>对照组。右颈总动脉的C-IMT(%)值在重叠组中最高,在对照组中最低。比较IH组和肺气肿组时无统计学差异。

结论

无论IH和肺气肿暴露在机制上是否协同,这种重叠都会引发更严重的全身/内皮炎症和内皮损伤;同时,证明了EPC的强力动员,但这并不意味着有强大的黏附及修复能力。

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