mAb2G4引导NF-κB诱骗性寡核苷酸对缺血心肌靶向保护作用的实验研究

项目名称： mAb2G4引导NF-κB诱骗性寡核苷酸对缺血心肌靶向保护作用的实验研究

项目编号： No.81201499

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 吴云

作者单位： 武汉大学

项目金额： 24万元

中文摘要： 心肌缺血再灌注损伤（MIRI）是阻碍缺血心肌从再灌注疗法中获得最佳疗效的主要难题。近年有研究报道抗肌球蛋白单克隆抗体(anti-myosin monoclonal antibody 2G4， mAb2G4)能高效特异性地与受损心肌细胞相结合；我们前期研究发现，核转录因子-κB诱骗性寡核苷酸(NF-κB decoy ODN)可减轻MIRI。因此，我们设想建立大鼠体外心肌细胞缺氧复氧模型和在体心肌缺血再灌注损伤模型，运用基因工程技术将mAb2G4和NF-κB decoy ODN融合成脂质体复合物（mAb2G4/ODN/lip），通过不同处理时间、处理途径的比较分析来探讨mAb2G4/ODN/lip是否能利用mAb2G4与缺血心肌细胞特异性相结合的特性，将NF-κB decoy ODN靶向导入受损心肌，通过抑制NF-κB诱导的炎性反应来保护心肌；为临床靶向治疗MIRI提供一定的理论和实践依据。

中文关键词： NF-κB；诱骗寡核苷酸；阳离子脂质体；心肌细胞；细胞低氧

英文摘要： The myocardial ischemia reperfusion injury (MIRI) is a main interference in the reperfusion therapy for acute myocardial infarction. The treatment of myocardial ischemia using gene therapy is a rather novel but promising approach.Recently, investigations have demonstrated that anti-myosin monoclonal antibody 2G4 (mAb2G4) specific toward cardiac myosin for targeted gene delivery to ischemic myocardium.In our study we also found that NF-κB decoy ODN could reduce myocardial reperfusion injury in rats.So we intend to establish the neonatal SD rats' myocardial cell hypoxia-reoxygenation model and myocardial ischemia reperfusion injure model by ligaturing anterior descending branch of left coronary artery for 30 minutes and perfusing for 120 minutes in rats.Genetic engineering technique was applied to construct a new kind of liposome complex: anti-myosin mAb2G4/ NF-κB decoy ODN / liposome complex( mAb2G4/ODN/lip). We will investigate by different treatment pathways and treatment times whether NF-κB decoy ODN could be targeted introduced into injured heart cells in rats beacause that mAb2G4 has specific binding to ischemic myocyte. And we will also explore whether mAb2G4/ODN/lip could reduce the MIRI by inhibiting the transcription of NF-κB. We believe that our research achievements can provide theoretical and pract

英文关键词： NF-kappaB；Decoy oligodeoxynucleotide；Cationic liposome；cardiomyocytes；Cell hypoxia