慢性间歇低氧对颏舌肌线粒体融合和分裂的影响以及脂联素的干预机制

The dysfunction of upper airway dilating muscles such as genioglossus is one of the important pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS). Our previous study demonstrated that chronic intermittent hypoxia (CIH) could induce mitochondrial dysfunction of genioglossal cells so that weakened contractility of genioglossus occured, while adiponectin supplement could significantly improve the above damages. However, the detailed mehanisms have not been completely elucidated. The balance of mitochondrial fusion-fission plays an important role in maintaining normal functions of mitochondrium. It has been reported that hypoxia/reoxygenation could cause imbalance of mitochondrial fusion-fission in myocardiocytes and further lead to mytochondrial dysfunction. Another study also showed that inhibition of mitochondrial could significantly reduce the myocardial ischemic reperfusion injury. Our previous research also found there was imbalance of mitochondrial fusion-fission under CIH, which manifested as increased abnormal fission, a key cause for mitochondrial dysfunction. Therefore, we speculate that it is highly possible that there is a close association between CIH-induced genioglossal mitochondrial dysfunction and imbalance of mitochondrial fusion-fission. Through investigation the correlation between them and the mechanism of adiponectin intervention, it is helpful to further elucidate the pathogenesis of OSAHS and provide theoretic proof for novel OSAHS drugs.

上气道扩张肌（如颏舌肌）功能受损是阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的重要发病机制。我们前期研究表明，慢性间歇低氧(CIH)诱导颏舌肌细胞线粒体功能紊乱，以致颏舌肌收缩力减弱；脂联素干预显著改善上述病理损伤。然而具体机制未完全阐明。线粒体融合-分裂平衡对维持线粒体功能至关重要。研究发现缺氧/复氧可致心肌细胞线粒体融合障碍，导致线粒体功能受损。另一研究表明，抑制线粒体分裂可显著减轻缺血/再灌注所致的心肌损伤。我们前期研究发现：CIH下，颏舌肌线粒体融合-分裂失衡，主要表现为线粒体异常分裂增加，而线粒体异常分裂又是导致线粒体功能障碍的重要原因，因此我们推断：CIH所致颏舌肌线粒体损伤和收缩力降低极可能与线粒体融合-分裂失衡相关。本课题通过探讨线粒体融合-分裂与CIH所致线粒体损伤之间的关系以及脂联素的干预机制，有助于进一步阐明OSAHS的发病机制，为将来研发新药提供理论依据。

上气道扩张肌(如颏舌肌)功能受损是阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的重要发病机制，然而损伤机制未完全阐明。我们通过建立慢性间歇低氧（CIH）大鼠模型，研究CIH对大鼠颏舌肌线粒体结构和功能的影响，同时观察脂联素的干预作用。研究发现，CIH下大鼠颏舌肌线粒体分裂异常增多，线粒体功能显著受损；当给与外源性脂联素后，可以显著减轻CIH诱导的颏舌肌线粒体异常分裂，改善CIH下线粒体功能。本研究结果有助于进一步阐明OSAHS所致上气道扩张肌损伤机理，为临床使用脂联素减轻OSAHS下上气道扩张肌损伤提供理论依据。围绕该课题，已发表SCI论文2篇。