Txnip对慢性间歇低氧致血管内皮细胞线粒体依赖性凋亡的调节机制研究

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）致心血管损伤机制是近年研究热点。慢性间歇低氧（CIH）所致氧化应激为关键病理生理机制。线粒体是氧化应激发生的重要场所，参与ROS生成及凋亡调控。硫氧还蛋白交互作用蛋白（Txnip）为重要的氧化抗氧化复合体组份，其可抑制硫氧还蛋白（TRX）的抗氧化与抗凋亡作用，也可作用于线粒体，影响其有氧呼吸功能及有氧无氧代谢转换，调节ROS生成。针对缺血再灌注心肌细胞损伤的研究发现Txnip促进线粒体依赖性凋亡在损伤中的作用，我们前期研究也证实Txnip为CIH致细胞损伤关键因子。但是，氧化应激（如CIH）下Txnip如何引起线粒体功能障碍及调节凋亡尚不清楚。因此，本课题拟在CIH动物和细胞模型上，深入研究Txnip对血管内皮细胞线粒体功能及线粒体相关凋亡的影响及机制。对全面阐述OSAHS致心血管损伤机制具有重要意义，并为寻找相关治疗靶点及药物开发奠定基础。

The mechanistic study of obstructive sleep apnea hypopnea syndrome (OSAHS)-related cardiovascular injury has been becoming a hot issue in recent years. Chronic intermittent hypoxia (CIH)-induced oxidative stress plays a pivotal role in this pathophysiological process. Mitochondria are not only an important organelle generating oxidative stress, but also involved in the regulation of ROS generation and apoptosis. Thioredoxin-interacting protein (Txnip), as an important component of antioxidant system, acts not only as an inhibitor against the antioxidant and anti-apoptotic roles of thioredoxin (TRX), but also a direct regulator of ROS production via affecting aerobic respiration in mitochondria and aerobic/anaerobic metabolic switch. Studies on ischemia-reperfusion injury of myocardial cells suggested that Txnip promoted mitochondrial-dependent apoptosis. Our previous study also confirmed Txnip as a critical factor in CIH-induced cell injury. However, the mechanisms of Txnip-mediated mitochondrial dysfunction and apoptosis caused by oxidative stress (e.g. CIH) still remain unclear. Therefore, this research will lucubrate the underlying mechanism of Txnip in affecting mitochondrial functions and mitochondrial-dependent apoptosis by using animal and cellular vascular endothelial injury models under CIH .To explore the relationship between Txnip and mitochondrial apoptosis under CIH will be meaningful to clarify the specific mechanisms of OSAHS related cardiovascular complications, and provide the basis for further studies of targeted drug.