水通道蛋白3在硬皮病小鼠氧化应激及纤维化中的作用

项目名称： 水通道蛋白3在硬皮病小鼠氧化应激及纤维化中的作用

项目编号： No.81460473

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 罗婧莹

作者单位： 桂林医学院

项目金额： 45万元

中文摘要： 组织器官纤维化是硬皮病患者死亡的主要原因。TGF-β及其下游细胞因子表达增高与成纤维细胞的活化密切相关。近来研究发现本病存在氧化应激障碍，改变细胞内活性氧(ROS)浓度可能改变细胞内TGF-β等细胞因子。H2O2作为重要的ROS可能通过水通道蛋白3(AQP3)转运，抑制AQP3的表达有望减少细胞内H2O2浓度，从而抑制TGF-β等细胞因子表达，最终抑制纤维化过程。本研究拟通过建立博来霉素硬皮病小鼠模型，分离培养原代小鼠皮肤成纤维细胞，并构建AQP3小分子 RNA干扰质粒，检测外源性H2O2及AQP3RNA干扰对硬皮病成纤维细胞AQP3、TGF-β等细胞因子及胶原I、III表达的影响,阐述AQP3在硬皮病氧化应激及纤维化中的重要作用。本研究有望为硬皮病治疗提供新靶点。

中文关键词： 水通道蛋白3；硬皮病；氧化应激；纤维化

英文摘要： The fibrosis of tissue and organ is the leading cause of death in patients with scleroderma. The increasing expressions of TGF-β and its downstream cytokines are closely related to fibroblast activation. Recent investigations have suggested that oxidative stress plays a role in scleroderma and that changing intracellular reactive oxygen species（ROS）may chang the expressions of TGF-β and its downstream cytokines. H2O2 as an important ROS may be transported by AQP3.Inhibiting the expression of AQP3 is expected to reduce the concentration of intracellular H2O2, thereby inhabit the expressions of TGF-β and other cytokines and finally inhabit fibrosis.In this study, we will establish the bleomycin-induced scleroderma mouse model, primarily culture mouse skin fibroblasts, build of AQP3 small molecules RNA interference plasmids, and then detect the expressions of AQP3 and fibrosis-related cytokines such as TGF-β and collagen I, III before and after H2O2 treatment and AQP3RNA interference in fibroblasts, in order to demonstrate that AQP3 plays an important role in oxidative stress and fibrosis in scleroderma. This study is expected to provide a new target for the treatment of scleroderma.

英文关键词： AQP3;scleroderma;oxidative stress;fibrosis