候选microRNAs调控泛素蛋白酶体系统影响心肌重构实验研究

项目名称： 候选microRNAs调控泛素蛋白酶体系统影响心肌重构实验研究

项目编号： No.81200158

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： 魏丽萍

作者单位： 天津市人民医院

项目金额： 23万元

中文摘要： 未能血运重建的缺血性心脏病患者进行性心肌重构、心功能下降是棘手的治疗难题，其病理基础主要是心肌细胞凋亡及心肌纤维化。MicroRNs是在转录后水平调控基因表达的细胞内非编码小RNA，在心力衰竭病程进展中起着上游调控的作用。泛素－蛋白酶体系统(Ubiquitin-proteasome system，UPS)在病损心肌中是高表达的，执行清除损伤或陈旧蛋白质, 参与DNA修复等下游调控作用。这两个起始及终末调控系统在进展性心肌重构中的相互作用及可能的影响，目前并无良好回答。此项研究将采用反义寡核苷酸阻断及构建病毒载体过表达等方法调节几种候选miRNAs表达并观察miRNAs通过UPS调控心肌重构的作用及可能机制,最终提出候选miRNAs通过干扰UPS系统相关mRNA而影响其蛋白合成从而影响心肌细胞凋亡、心肌纤维化进程，反义寡核苷酸阻断技术将成为一种新的抑制心肌重构的方法。

中文关键词： MicroRNAs；泛素蛋白酶体系统；缺血性心脏病；凋亡；

英文摘要： Ischemia heart disease represents the primary cause of human morbidity and mortality. Especially those patients who didn't accepted coronary vascular reconstruction display a dynamic myocardium remodeling and deceasing heart function. It is formidable to seek perfect therapeutic strategy for those patients. The pathological process of ischemic heart is myocardium remodling associated with myocardial cell apoptosis and myocardial fibrosis. The implications of miRNAs in the pathological process of cardiovascular system have recently been recognized. MicroRNAs are endogenous, no encoding small RNA regulating the post- transcription of target gene, which play upstream regulation action in pathogenesis of heart failure. Ubiquitin-proteasome system (UPS) is high expression in impaired myocardium, responsible for the degradation of majority of impaired and olden cellular proteins and playing essential roles in DNA repair. MicroRNA control gene expression in transcriptional and post-transcriptional level and UPS regulate cell apoptosis in protein and translation level. However, without satisfy reply about the relationship between the two important systems up now. According to our previous work demonstrated that candi

英文关键词： MicoRNAs；UPS；Ischemia heart disease；Apoptosis；