新型过氧化物酶Prx-2在高血压心功能下降和心力衰竭中的保护作用

项目名称： 新型过氧化物酶Prx-2在高血压心功能下降和心力衰竭中的保护作用

项目编号： No.81200188

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 孙影

作者单位： 河北联合大学

项目金额： 24万元

中文摘要： 心力衰竭是高血压致死的主要原因之一，活性氧物质（reactive oxygen species，ROS）对此有重要促进作用。ROS可直接引起心肌细胞坏死，也可通过信号转导通路促进心肌细胞凋亡，从而使心肌细胞数量减少，导致心功能下降和心力衰竭，因此降低ROS水平及抑制其作用通路可有效防治心功能下降和心力衰竭。Peroxiredoxin-2（Prx-2）是一种新型过氧化物酶，与其它过氧化物酶不同的是，Prx-2可通过调控ROS水平参与信号转导，从而影响细胞增殖、分化和凋亡。Prx-2在多种疾病中均呈细胞保护作用，但在高血压心脏病方面未见报道。本项目首先检测Prx-2在高血压心脏中的表达，然后利用高表达Prx-2的转基因小鼠，观察Prx-2对高血压心功能下降和心力衰竭的影响，探讨Prx-2是否通过降低ROS及其介导的细胞死亡发挥心脏保护作用，为Prx-2成为治疗新靶点提供重要的理论和实验依据。

中文关键词： 2K-1C；DOCA-Salt；peroxiredoxin 2；活性氧；凋亡

英文摘要： The main reasons to death in patients with hypertension are cardiac dysfunction and heart failure, in which reactive oxygen species (ROS) play an important role. The detrimental effect of ROS are mediated with both cardiomyocyte necrosis caused by oxidation of lipids, proteins and DNA and apoptosis by activation of intracellular signaling pathways, leading to the decrease in total cell numbers. Therefore, reduction of ROS prevents hypertension-induced heart dysfunction and heart failure. Peroxiredoxin-2 (Prx-2), a member o Prx family, is recently found to have antioxidant activity and protective effect in many diseases. However, the role in hypertension-induced cardiac dysfunction and heart failure is not clear. This project will firstly detect the expression of Prx-2 in heart with hypertension caused by different reasons, and then detect the effect of Prx-2 on cardiac dysfunction and heart failure using transgenic mice with Prx-2 overexpression, finally explore whether the cardioprotective effect of Prx-2 is through ROS and ROS-induced cell necrosis and apoptosis. The significance of the study is is to explore the new ways to treat and prevent cardiac dysfunction and heart failure in hypertension and provide some important theories and experimental evidence for Prx-2 as a new target for clinical treatment.

英文关键词： 2K-1C；DOCA-Salt；peroxiredoxin 2；ROS；apoptosis