ROS/MAPK/MMP信号通路在阻塞性睡眠呼吸暂停相关血管重构中的作用机制研究

血管重构是重大心脑血管疾病发展的关键步骤。阻塞性睡眠呼吸暂停（OSA）可促进血管重构，但分子机制不清，缺乏针对性干预措施。我们前期研究发现慢性间断性缺氧（CIH）和OSA（CIH+胸膜腔内压改变）不同程度的促进MMP表达和胶原沉积。MMP具有促血管重构作用，但其参与OSA相关血管重构的分子机制不清。活性氧（ROS）可激活丝裂原活化蛋白激酶（MAPK）信号通路促进MMP表达，故我们推测CIH导致氧化应激产生ROS通过MAPK信号通路激活MMP，而OSA胸膜腔内压改变也可能加重该过程。本研究拟通过观察OSA和CIH状态下血管中膜MMP和MAPK信号通路相关基因表达情况，确认OSA和CIH对MMP表达的影响及其在血管重构中的作用，揭示并验证该状态下ROS/MAPK/MMP信号通路的分子机制，确定干预该通路对抑制OSA相关血管重构的效应，为OSA相关血管重构的防治靶点提供理论依据。

Vascular remodeling is the key step in the development of major cardiovascular and cerebrovascular diseases. Obstructive sleep apnea (OSA) promotes vascular remodeling. However, the specific molecular mechanism of how OSA causes vascular remodeling remains unclear. So, there is a lack of targeted interventions. Our previous studies showed that chronic intermittent hypoxia (CIH) and OSA (CIH+ intrapleural pressure change) promoted the expression of MMP and collagen deposition in different degrees. MMP is known to promote vascular remodeling, but whether it is involved in OSA induced vascular remodeling and its molecular mechanism remains unclear. Reactive oxygen species (ROS) can promote the expression of MMP and increase its effect by activating the mitogen-activated protein kinase (MAPK) signaling pathway. Thus, we hypothesized that CIH causes oxidative stress to produce ROS and activate MMP through MAPK signaling pathway and promote vascular remodeling, besides, the change of intrapleural pressure of OSA may also be involved in this process. This study will observe the expression of MMP and MAPK signaling pathway related genes in the vascular media to confirm the effect of OSA and CIH on MMP expression and its role in vascular remodeling, reveal and verify the molecular mechanism of ROS/MAPK/MMP signaling pathway in OSA and CIH status. This study will provide a theoretical basis for the prevention and treatment of OSA-induced vascular remodeling.