Cys C/Wnt通路在高龄急性心肌梗死心肌损伤中的作用及新机制

项目名称： Cys C/Wnt通路在高龄急性心肌梗死心肌损伤中的作用及新机制

项目编号： No.81500269

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 付振虹

作者单位： 中国人民解放军总医院

项目金额： 18万元

中文摘要： 我国高龄人口迅速增长，高龄急性心肌梗死（AMI）患者心功能受损严重、预后差，明确高龄AMI患者心肌损伤加重机制意义重大。申请人研究发现，高龄AMI患者血清胱抑素C(Cys C)明显升高且与心功能下降相关，是高龄AMI患者死亡的独立危险因素。有研究显示，Cys C导致心肌细胞凋亡和心肌损伤加重，但具体机制不明确。本项目拟在前期研究基础上，建立高龄小鼠AMI和缺氧衰老心肌细胞模型，分别在动物整体水平和细胞分子水平，采用基因沉默和过表达方法，观察Cys C表达变化与高龄AMI心肌损伤间的关系，Cys C/Wnt通路活化对心肌细胞凋亡、血管新生和纤维化、心功能和存活率的影响，进一步探讨Cys C在高龄和衰老状态下对心肌合成Wnt/β-catenin调节作用的机制。本项目通过探索临床高龄AMI患者心肌损伤新机制，为临床治疗提供新的实验依据和防治靶点。

中文关键词： 急性心肌梗死；心肌损伤；高龄；胱抑素C；Wnt

英文摘要： Acute myocardial infarction (AMI) is a serious threat to the health of Chinese people. Chinese elderly population is growing rapidly. The cardiac function is injured seriously and the prognosis is poor in elderly AMI patients. It is very important to make clear the inherent mechanism of myocardial injury aggravation in elderly AMI patients. Our previous research found that the level of serum cystatin C (Cys C) increased significantly, which was associated with deterioration of heart function and was an independent risk factor of death in elderly AMI patients. Some papers indicated that Cys C causethe apoptosis of myocardial cells and myocardial injury. But the specific molecular mechanism is not clear. On the basis of previous research, the present study is planed to be done as follows: first, establish an AMI model in elderly mice and a hypoxia myocardial cells model in aging cells; then, in the whole animal model level and cell molecular level respectively, using the gene silencing and over expression method, observe the relationship between the level of Cys C expression and myocardial injury in elderly AMI models, and the impacts of Cys C/ Wnt pathway activation on cardiomyocyte apoptosis, angiogenesis and fibrosis, cardiac function and survival rate; and further investigate the regulating mechanism of Cys C on synthesis of Wnt/ beta –catenin protein in aged and aging conditions. Our project will provide a new experimental evidence and prevention target point for elderly AMI clinical treatment by investigating the new mechanism of myocardium injury in elderly AMI patients.

英文关键词： acute myocardial infarction;myocardial injury;very elderly;cystatin C;Wnt