“养阴清肺活血”法干预放射性肺损伤Notch信号调控Th17/Treg平衡的机制研究

项目名称： “养阴清肺活血”法干预放射性肺损伤Notch信号调控Th17/Treg平衡的机制研究

项目编号： No.81473462

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 侯炜

作者单位： 中国中医科学院广安门医院

项目金额： 74万元

中文摘要： 放射性肺损伤(RILI)发生机制比较复杂，其中免疫失衡机制虽提出不久，但逐渐被学界重视，研究表明RILI微环境中免疫相关细胞因子存在异常表达，Th1/Th2失衡也已被证实在RILI中发挥了重要作用。最新研究显示Th17/Treg平衡也可能在RILI的发生发展中扮演了重要角色，而Notch信号则是调控T细胞增殖、分化以及各种免疫功能的重要信号转导系统。中药养阴清肺活血法治疗RILI疗效显著,可多靶点有效改善机体免疫功能，尤其对于各种免疫失衡具有显著的调节作用。所以课题通过建立RILI（放射性肺炎和放射性肺纤维化）大鼠模型，研究RILI外周血和肺组织局部存在Th17/Treg细胞失衡的特征，并进一步探讨这种失衡可能受到Notch信号通路调控；而通过养阴清肺活血法干预，初步探讨其对RILI的作用及对Notch信号调控Th17/Treg平衡复杂网络的影响机制，为中药新药开发应用提供依据。

中文关键词： 中医药；放射性肺损伤；Th17/Treg平衡；Notch信号通路；分子机制

英文摘要： Mechanisms of radiation-induced lung injury (RILI) is complicated, although the mechanism of immune imbalance was proposed soon, but has gradually taken seriously academia, many studies have shown that the presence of abnormal expression of immune-related cytokine in microenvironment of RILI, and Th1/Th2 imbalance has been confirmed played an important role in radiation pneumonitis and pulmonary fibrosis radioactive.Studies have shown that Th17/Treg balance may also play an important role in the development of RILI, while the Notch signal is an important signal transduction system in the regulation of T cell proliferation, differentiation and immune function.Traditional Chinese medicine can effectively improve the immune function with multiple targets, especially for a variety of immune imbalance has significant regulatory role.So this project on the basis of pre-clinical and experimental research, through the establishment of RILI (radiation pneumonitis and pulmonary fibrosis radioactivity) rat model, study the presence Th17/Treg imbalance characteristics in the peripheral blood and lung tissue localized of RILI from the perspective of the body，and to further explore this imbalance may be mainly regulated by Notch signaling pathway. While intervention by traditional Chinese medicine Yangyin Qingfei, preliminary study on the role of Chinese herbs in RILI and its influence on complex networks that the regulation of Notch signaling mechanism in Th17/Treg balancing, to provide the experimental basis for the further development and application of new drugs of traditional Chinese medicine, also for the benefit of patients.

英文关键词： Traditional Chinese medicine;radiation-induced lung injury;Th17/Treg balance;Notch signaling pathway;molecular mechanisms