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慢性间歇性低氧对小鼠右心室的时序性改变

Chronological Change of Right Ventricle by Chronic Intermittent Hypoxia in Mice.

机构信息

Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.

The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Sleep. 2017 Aug 1;40(8). doi: 10.1093/sleep/zsx103.

DOI:10.1093/sleep/zsx103
PMID:28637196
Abstract

STUDY OBJECTIVE

No studies have investigated sequential changes in the heart on magnetic resonance imaging (MRI), along with observation of functional lung phenotypes and genetics, over the duration of chronic intermittent hypoxia (CIH). We investigated chronological changes in heart and lung phenotypes after CIH using a mouse model to provide new insights into the pathophysiology of sleep apnea-induced cardiovascular disease.

METHODS

C57BL/6J adult male mice were randomized to 4 or 8 weeks of CIH. Cardiac cine-MRI images were analyzed to assess functional parameters of right ventricle (RV). Histopathological features of myocytes and pulmonary vessels, as well as genes involved in the endothelin (ET) system, were investigated.

RESULTS

Function of the RV reduced significantly at 4 weeks and continuously decreased following another 4 weeks of CIH, although the rate of decrease was attenuated. Notably, persistence of reduced ejection fraction and end-systole RV wall thickness (WT) and increases in the ET system of the lungs and blood strongly implied the development of pulmonary hypertension after 8 weeks of CIH.

CONCLUSIONS

RV dysfunction with reduced end-systole RV WT could be a late phenotype in long-standing CIH and possibly also in obstructive sleep apnea.

摘要

研究目的

目前尚无研究探讨慢性间歇性低氧(CIH)期间心脏磁共振成像(MRI)的连续变化,以及肺功能表型和遗传学的观察。我们使用小鼠模型研究了 CIH 后心脏和肺表型的时间变化,为睡眠呼吸暂停引起的心血管疾病的病理生理学提供了新的见解。

方法

将成年雄性 C57BL/6J 小鼠随机分为 4 或 8 周的 CIH 组。对心脏电影 MRI 图像进行分析,以评估右心室(RV)的功能参数。研究心肌细胞和肺血管的组织病理学特征,以及涉及内皮素(ET)系统的基因。

结果

RV 的功能在 4 周时明显降低,并且在另外 4 周的 CIH 后持续下降,尽管下降速度减弱。值得注意的是,射血分数降低和收缩末期 RV 壁厚度(WT)持续减少以及肺和血液中 ET 系统增加强烈暗示 8 周 CIH 后发生了肺动脉高压。

结论

收缩末期 RV WT 减少的 RV 功能障碍可能是长期 CIH 甚至阻塞性睡眠呼吸暂停的晚期表型。

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