活性氧介导的内质网应激在博莱霉素诱发肺上皮-间质转化和肺纤维化中的作用

项目名称： 活性氧介导的内质网应激在博莱霉素诱发肺上皮-间质转化和肺纤维化中的作用

项目编号： No.81670060

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 赵卉

作者单位： 安徽医科大学

项目金额： 25万元

中文摘要： 前期研究发现博莱霉素致小鼠肺纤维化过程伴有肺上皮内质网应激。本课题拟深入研究活性氧在博莱霉素诱发小鼠肺上皮内质网应激过程的作用；用TUDCA抑制小鼠肺上皮内质网应激，观察TUDCA对博莱霉素所致肺上皮间质转化和纤维化的拮抗效应，阐明活性氧介导的内质网应激在肺上皮间质转化和纤维化过程的作用；用4μ8C选择性抑制IRE1核糖核酸酶活性，观察体内IRE1核酸酶抑制剂对博莱霉素所致肺上皮间质转化和肺纤维化的拮抗作用，阐明内质网应激IRE1通路介导肺上皮间质转化和纤维化的机制。本课题为阐明肺纤维化发病机制提供理论依据。

中文关键词： 内质网应激；上皮-间质转化；肺纤维化；活性氧；博莱霉素

英文摘要： Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells plays a key role in pulmonary fibrosis. Previous study observed endoplasmic reticulum (ER) stress in the process of bleomycin-induced pulmonary fibrosis in mice. This project will explore the role of reactive oxygen species (ROS) in bleomycin-induced ER stress. To explore the role of ROS-mediated ER stress on bleomycin-induced EMT and pulmonary fibrosis, mice are pretreated with TUDCA, a chemical chaperone, to inhibit ER stress in mice lungs.. We then observe the antagonistic effect of TUDCA pretreatment on bleomycin-induced EMT and pulmonary fibrosis. To explore the role of IRE1 pathway on bleomycin-induced EMT and pulmonary fibrosis, 4μ8C, an IRE1 specific RNase inhibitor, is injected to inhibit IRE1 RNase activity in mouse lungs. We then observe the inhibitive effect of IRE1 RNase inhibitor on bleomycin-induced EMT and pulmonary fibrosis. This project will provide the basis for the pathogenesis of pulmonary fibrosis in human beings.

英文关键词： ER stress;epithelial-mesenchymal transition ;pulmonary fibrosis;reactive oxygen species;bleomycin