Huang Hanpeng, Jiang Xiufeng, Dong Yanbin, Zhang Xiaofeng, Ding Ning, Liu Jiannan, Hutchinson Sean Z, Lu Gan, Zhang Xilong
Department of Respirology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Department of Respirology, Nanjing Medical University affiliated Wuxi People's Hospital, Wuxi, China.
PLoS One. 2014 Oct 20;9(10):e109284. doi: 10.1371/journal.pone.0109284. eCollection 2014.
Genioglossal dysfunction is involved in the pathophysiology of obstructive sleep apnea hypoxia syndrome (OSAHS) characterized by nocturnal chronic intermittent hypoxia (CIH). The pathophysiology of genioglossal dysfunction and possible targeted pharmacotherapy for alleviation of genioglossal injury in CIH require further investigation.
METHODOLOGY/PRINCIPAL FINDINGS: Rats in the control group were exposed to normal air, while rats in the CIH group and CIH+adiponectin (AD) group were exposed to the same CIH condition (CIH 8 hr/day for 5 successive weeks). Furthermore, rats in CIH+AD group were administrated intravenous AD supplementation at the dosage of 10 µg, twice a week for 5 consecutive weeks. We found that CIH-induced genioglossus (GG) injury was correlated with mitochondrial dysfunction, reduction in the numbers of mitochondrias, impaired mitochondrial ultrastructure, and a reduction in type I fibers. Compared with the CIH group, impaired mitochondrial structure and function was significantly improved and a percentage of type I fiber was elevated in the CIH+AD group. Moreover, compared with the control group, the rats' GG in the CIH group showed a significant decrease in phosphorylation of LKB1, AMPK, and PGC1-α, whereas there was significant rescue of such reduction in phosphorylation within the CIH+AD group.
CIH exposure reduces mitochondrial biogenesis and impairs mitochondrial function in GG, while AD supplementation increases mitochondrial contents and alleviates CIH-induced mitochondrial dysfunction possibly through the AMPK pathway.
颏舌肌功能障碍参与阻塞性睡眠呼吸暂停低氧综合征（OSAHS）的病理生理过程，该综合征以夜间慢性间歇性缺氧（CIH）为特征。颏舌肌功能障碍的病理生理学以及缓解CIH中颏舌肌损伤的可能靶向药物治疗需要进一步研究。
方法/主要发现：对照组大鼠暴露于正常空气中，而CIH组和CIH+脂联素（AD）组大鼠暴露于相同的CIH条件下（连续5周，每天CIH 8小时）。此外，CIH+AD组大鼠静脉注射AD补充剂，剂量为10μg，每周两次，连续5周。我们发现CIH诱导的颏舌肌（GG）损伤与线粒体功能障碍、线粒体数量减少、线粒体超微结构受损以及I型纤维减少有关。与CIH组相比，CIH+AD组线粒体结构和功能受损明显改善，I型纤维百分比升高。此外，与对照组相比，CIH组大鼠的GG中LKB1、AMPK和PGC1-α的磷酸化显著降低，而CIH+AD组中这种磷酸化降低得到了显著挽救。
暴露于CIH会减少GG中的线粒体生物合成并损害线粒体功能，而补充AD可增加线粒体含量并可能通过AMPK途径减轻CIH诱导的线粒体功能障碍。
