放射性肺纤维化（RILF）发生机制尚未阐明。抗氧化应激关键信号分子Nrf2参与RILF发生、发展，但具体机制不清。我们前期研究发现：三萜类药物CDDO-Me诱导Nrf2过表达可调控TGF-β1/Smad3信号通路，缓解RILF。本研究拟进一步探讨，Nrf2对TGF-β1/Smad3信号通路调控的具体机制。本研究通过体内、外实验，观察上调或干扰Nrf2，对氧化应激、TGF-β1/Smad3信号通路的影响；证实Nrf2介导抗氧化应激，抑制Latent TGF-β1激活，降低TGF-β1水平；并证明，Nrf2直接与Smad3基因5'调控区位点结合，抑制Smad3转录，进而影响下游纤维化相关信号分子PAI-1、α SMA和collagen I的水平，揭示Nrf2调控TGF-β1/Smad3信号通路参与RILF的机制。本研究有助于阐明RILF的发生机制，为发现RILF治疗新方法提供实验依据。

The molecular mechanisms of radiation induced lung fibrosis (RILF) are poorly understood. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an antioxidant-activated transcription factor that recently emerged as a critical regulator of cellular defense against oxidative and contributes significantly to the pathogenesis of RILF. In our previous study, we found that triterpeniod CDDO-Me could activate Nrf2. The up-regulated Nrf2 suppressed fibrosis related proteins plasminogen activator inhibitor-1 (PAI-1), αsmooth muscle actin (αSMA), and collagen I and ameliorated RILF through TGF-β1/Smad3 pathway. In this study, we attempt to explore the molecular mechanism of regulation of TGF-β1/Smad3 signaling pathway by Nrf2 in the pathogenesis of RILF. The hypothesis will be tested in both in vitro and in vivo studies. We will investigate the impact of Nrf2 expression levels on ROS-mediated activation of latent TGF-β1 firstly. And then, the study will find that Nrf2 can bind to the 5' regulation region of Smad3 and suppress its transcription. After that, we will try to explain the molecular mechanism of Nrf2 regulated TGF-β1/Smad3 pathway in the pathogenesis of RILF. This study will disclose a potential regulatory mechanism in RILF that will aid the development of new therapies.