晚期糖基化终末产物受体参与急性呼吸窘迫综合征细胞外基质重塑的机制

急性呼吸窘迫综合征（ARDS）病死率高，发病机制复杂。在ARDS的肺修复过程中，细胞外基质（ECM）的重塑是影响ARDS预后的主要因素。研究表明晚期糖基化终末产物受体（RAGE）参与了ARDS发生发展过程中，但RAGE是如何参与ARDS后ECM重塑的机理，尚不明了。本课题利用脂多糖（LPS），构建肺上皮细胞和实验动物的ARDS模型，应用RT-PCR、免疫蛋白印记和激光共聚焦显像等技术，研究ARDS细胞和动物模型的MAPKs/NFκB信号通道的激活、RAGE表达、金属基质蛋白酶/金属基质蛋白酶抑制物（MMPs/TIMPs）激活和降解之间的相互作用关系，探索ARDS过程中RAGE、MMPs/TIMPs参与肺ECM重塑的调控机制，为治疗ARDS提供相应的理论依据。

Acute respiratory distress syndrome (ARDS) has high mortality and its mechanism is complex. The prognosis is affected by the repair process such as fibrosis of alveolar cells and remodeling of extracellular matrix (ECM). The receptor of advanced glycation end products (RAGE) is involved in the progress of ARDS. The regulation mechanism of RAGE in ECM remodeling in ARDS is not fully understood. The experiments are performed both on lung epithelial cells and in LPS-induced ARDS animal model in order to figure out the relationship among RAGE, matrix metalloproteinase/metal matrix protease inhibitors (MMPs/TIMPs) and ECM remodeling. RT-PCR, western blotting, confocal microscope and other technologies are used to measure the activation of MAPKs/NFκB pathway, and the expression of RAGE, MMPs/TIMPs following the stimulation, to determine the cross talk and interaction of RAGE, MMPs/TIMPs and ECM remodeling during the procedure of ARDS. This study is designed to investigate the novel axis of RAGE- MMPs/TIMPs-ECM remodeling in ARDS, and provide a theoretical basis for the treatment of ARDS.