冷休克蛋白YB-1在主动脉夹层形成与发展中的分子机制研究

Aortic dissection (AD) is a potentially fatal vascular disease. The cold shock protein YB-1 is a highly conserved protein. Recent studies have shown that YB-1 is involved in the biological regulation of vascular endothelial cells, vascular smooth muscle cells and mononuclear macrophages that are closely related to the formation and development of AD. However, there is no report on the direct relationship between YB-1 and the formation and development of AD. Our preliminary study found that the expression of YB-1 and the oxidative stress in the aorta of AD patients and mouse models were significantly higher than those in the control group. Therefore, we suggest that the expression of YB-1 in aorta may be an important mechanism for the development of AD. The specific regulation of YB-1 may play a protective role against AD. In this study, we established the AD model ingenetically modified mice to study the relationship between YB-1 and AD, and to explore how YB-1 can play a role in mitochondrial redox state in specific cells involved in the development of AD, and to explore whether exogenous regulation of YB-1 protects AD from in vivo experiments and provide a new theoretical basis for.the precise prevention and control of AD.

主动脉夹层（aortic dissection, AD）是一种具有潜在致命性的血管性疾病。冷休克蛋白YB-1是高度保守的蛋白，最近研究表明YB-1参与了与AD形成和发展息息相关的血管内皮细胞、血管平滑肌细胞及单核巨噬细胞的生物学调控。然而目前未有研究报道YB-1与AD发生及发展的直接关系。我们的前期研究发现AD患者和小鼠模型的主动脉组织中YB-1的表达及氧化应激水平均显著高于对照组。故我们推测主动脉组织YB-1的表达增加可能是AD发生发展的一个重要机制，特异性的调控YB-1的表达可能对AD具有保护作用。本实验应用基因改造小鼠建立AD模型，研究YB-1与AD之间的关系以及调控机制，重点探讨YB-1是如何通过调控参与AD发生发展的特定细胞中线粒体氧化还原状态发挥其作用，并通过在体动物实验探索外源性调控YB-1是否对AD起保护作用，为AD的精准防治提供新的理论依据。

主动脉夹层（aortic dissection, AD）是一种具有潜在致命性的血管性疾病。冷休克蛋白YB-1是高度保守的蛋白，最近研究表明YB-1参与了与AD形成和发展息息相关的血管内皮细胞、血管平滑肌细胞及单核巨噬细胞的生物学调控。然而目前未有研究报道YB-1与AD发生及发展的直接关系。因此，阐明YB1在主动脉夹层发生发展中的作用对临床具有非常重要的意义。本研究采用血管紧张素II (Ang II) 诱导的野生型和主动脉内皮细胞特异性敲除YB1的小鼠主动脉夹层疾病模型首次证实了YB1在主动脉夹层发生发展中的重要作用, 其作用是在Ang II干预条件下，内皮细胞中YB1线粒体的转位减少；其磷酸化的YB1线粒体转位增加，从而增加了线粒体ROS的产生。本研究为治疗主动脉夹层提供新的思路和理论依据。