Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model

被引:50
作者
Wei, Qin [1 ,2 ]
Bian, Yeping [3 ]
Yu, Fuchao [1 ]
Zhang, Qiang [2 ]
Zhang, Guanghao [1 ]
Li, Yang [1 ,2 ]
Song, Songsong [1 ]
Ren, Xiaomei [4 ]
Tong, Jiayi [1 ,2 ]
机构
[1] Southeast Univ, Cardiovasc Inst, Nanjing 210009, Jiangsu, Peoples R China
[2] Southeast Univ, Zhongda Hosp, Dept Cardiol, Nanjing 210009, Jiangsu, Peoples R China
[3] Jiangsu Prov Official Hosp, Dept Intens Care Unit, Nanjing 210009, Jiangsu, Peoples R China
[4] Southeast Univ, Dept Geriatr, Zhongda Hosp, Nanjing 210009, Jiangsu, Peoples R China
关键词
obstructive sleep apnea; model chronic intermittent hypoxia; cardiac dysfunction; inflammation;
D O I
10.7555/JBR.30.20160110
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1 alpha, NF-kappa B, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1 alpha and NF-kappa B signaling molecules and development of cardiac inflammation, apoptosis and fibrosis.
引用
收藏
页码:490 / 495
页数:6
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