NADPH氧化酶和线粒体UCP2蛋白影响人气道平滑肌细胞氧化/抗氧化平衡的作用及机制

气道重塑是慢性阻塞性肺疾病（COPD）重要的病理改变，是引起COPD患者持续存在的气流受限的主要原因。小气道平滑肌细胞的增生、肥大以及细胞外基质的异常沉积是导致气道重塑的重要原因。研究表明转化生长因子超家族（TGF-β）可以通过诱导平滑肌细胞增生、肥大，细胞外基质沉积导致气道重塑。活性氧类（ROS）是激活TGF-β信号通路的重要诱因。目前，ROS激活TGF-β信号通路参与气道重塑的具体机制不明。我们前期研究发现TGF-β可以上调NADPH氧化酶（NOXs）促进细胞内ROS的产生；ROS可以上调线粒体解偶联蛋白UCP2的表达。本课题将深入研究：1、NOXs及UCPs在气道平滑肌细胞内源性ROS的产生中的作用；2、NOXs及UCPs对细胞氧化/抗氧化平衡以及细胞功能的影响及机制。力图阐明NOXs及UCPs参与气道重塑的作用机制，为进一步揭示COPD的发病机制，为COPD的防治提供理论依据。

The crucial pathologic feature of COPD is airway remodeling. The airway remodeling contribute to airflow obstruction of COPD. An increase in matrix deposition in adventitial compartments of the small airway and an increase in both the amount and the mass of airway smooth muscle cells has been described in patients with COPD, which contributes to airway remodeling. It has been recently shown that TGF-β induces airway smooth muscle cells proliferation, hypertrophy and release of angiogenic, fibrogenic which contribute to airway remodeling. ROS activate and/or mediate the effects of TGF-β. The mechanisms underlying such pathway of ROS-mediated TGF-β activation remain largely unknown. My previous work has implicated that H2O2 unregulated the expression of the NOXs, which is possible to promote the production of ROS. ROS upregulated the expression of UCP2.In this study 1.We investigate the effect of NOXs and UCPs in production of ROS.2.We investigate the role of NOXs and UCPs in disrupting oxidant/antioxidant balance and in inducing ASM proliferation. We want to determine whether NOXs and UCPs are involved in airway remodeling. This research may contribute to elucidate the cellular pathways that are critically involved in COPD pathogenesis and develop the better means of the prevention and treatment of COPD.