气道平滑肌细胞(ASMC)增殖是气道重塑发生、发展的关键环节，而且作为免疫细胞可合成和分泌炎症细胞因子加重炎症反应。研究认为Notch-1和HO-1是气道重塑的重要治疗靶点，可能受TLR4/mTOR以及TLR4/Nrf2信号通路的调控，形成TLR4/mTOR/Notch-1以及TLR4/Nrf2/HO-1信号网络。前期研究表明山茱萸新苷可调控肺组织中Notch-1和HO-1表达、提高抗氧化酶活性，防止气道重塑。但是上述信号通路与气道重塑以及山茱萸新苷干预的相关研究尚未见报道。 本课题拟通过ASMC和小鼠哮喘气道重塑模型，从分子、细胞和整体水平，以TLR4为切入点并延伸到下游mTOR和Nrf2途径，探讨山茱萸新苷介导TLR4/mTOR 及TLR4/Nrf2信号通路调节Notch-1和HO-1的作用机制，明确山茱萸新苷对此信号通路中的作用靶点，为寻找防治气道重塑以及新药开发提供有效的理论依据。

Airway smooth muscle cell (ASMC) proliferation is a major factor in airway remodeling. As immune cells ASMC increase inflammatory reaction by synthesize and secrete inflammatory cytokines. Notch-1 and HO-1 have been known as therapeutic targets of airway remodeling. They were contributed with regulating of TLR4/mTOR and TLR4/Nrf2 signaling pathways, which produces the network of TLR4/mTOR/Notch-1 and TLR4/Nrf2/HO-1.In the previous study, we demonstrated that cornuside suppressed the Notch1 and HO-1 expression in the lung, improved the antioxidant enzymes activity and prevented airway remodeling. But there were no reports on the roles of TLR4/mTOR/Notch-1 and TLR4/Nrf2/HO-1 signal pathway on airway remodeling or on its protective mechanism of cirnuside. In this study, we evaluate TLR4 mediated mTOR and Nrf2 activation in cultured ASMC and mice airway remodeling model. In addition, we examine suppressive effects on TLR4 mediated mTOR and Nrf2 in cultured ASMC and also on airway remodeling in mice model. Furthermore we evaluate the mechanism of suppressive effects of cirnuside on TLR4/mTOR/Notch-1 and TLR4/Nrf2/HO-1 signaling pathways. Through these molecular mechanisms, cirnuside may control the expression of Notch-1 and HO-1. This study may provide us new tools, such as cirnuside, contributing to prevention and therapy for airway remodeling and development of new kinds of drugs.