不同来源ROS在睡眠呼吸暂停模式间歇低氧诱发血管内皮损伤中的作用

Intermittent hypoxia of sleep apnea mode can induce oxidative stress, resulting in the production of large amounts of reactive oxygen species (ROS). NADPH oxidase and mitochondrial respiratory chain are the major sources of ROS. We have reported that IH could cause overexpression of NADPH oxidase, accompanied by MDA levels increased at the same time. The mechanism of vascular endothelial injury induced by ROS caused by intermittent hypoxia is becoming a hot research, and the interactions between the main cellular sources of ROS remain obscure. Our project is intended to study the mechanism of different sources of ROS effect on endothelial system induced by intermittent hypoxia and the cross talk between the sources of ROS. It will be clarified that ROS generated by NADPH oxidase and the mitochondrial respiratory chain produces different effects on vascular endothelial injury in the intermittent hypoxia. At last, we will use different sources ROS inhibitors or calcium antagonists to explore the therapeutic effect on vascular injury induced by intermittent hypoxia by clearing the different sources of ROS, and try to find a more effective prevention and treatment of cardiovascular complications in OSAHS.

睡眠呼吸暂停模式间歇低氧可以诱发氧化应激，产生大量ROS。NADPH氧化酶和线粒体呼吸链是ROS的主要来源，不同来源的ROS在间歇低氧导致血管内皮损伤中的作用机制有何不同以及它们之间的相互关系逐渐成为研究的热点。我们已经发表的研究显示NADPH氧化酶在间歇低氧暴露后表达增加，伴随着氧化应激指标的增高；但对于间歇低氧暴露后不同来源ROS产生的机制及对血管内皮的损伤机制尚不清楚，本申请项目拟在前述研究的基础上，通过对间歇低氧诱导下不同来源的ROS及其对内皮系统的影响进行研究，从而进一步明确NADPH氧化酶产生的ROS和线粒体呼吸链产生的ROS在间歇低氧刺激下对于血管内皮损伤的不同作用，并进一步探讨二者之间的相互作用机制；并通过应用不同来源ROS阻断剂或钙离子拮抗剂，探讨清除不同来源ROS对于间歇低氧诱发血管损伤的治疗作用，努力寻找更有效的预防和治疗OSAHS相关心血管并发症的药物。