几乎所有类型的心脏疾病都以心力衰竭为结果，然而心力衰竭内在的始发性因素及其分子机制至今不明。申请人筛选并克隆了在人类心力衰竭的心脏组织中具有显著性差异表达的基因Nmnat。尽管Nmnat生物学相关功能有被广泛报道, 但是其在体内心脏中的功能至今一无所知。申请人的前期研究结果提示Nmnat基因可能与成体心力衰竭的发生有关。本研究拟利用果蝇转基因模型，在时空上特异性的沉默成体心脏中的Nmnat基因，研究Nmnat基因与心力衰竭发生的关系、在心力衰竭反应过程中的作用、以及参与的心力衰竭信号途径等机制；进一步在本研究中心自主研发的果蝇运动装置基础上，将人体运动科学与遗传学相结合，探索和建立运动在心力衰竭中保护研究新的思维模式和新的防治理念。综上所述，本项目以心力衰竭为核心，围绕“病因—机制—防治”三方面展开研究，为人类关于运动对心力衰竭疾病的预防、检测和治疗提供理论依据和临床指导意见。

Almost all types of heart disease always end up with heart failure. However, the molecular mechanism which underlies this process and the primary cause of heart failure remain unknown. To reveal the molecular mechanisms of heart failure, the applicant have cloned a specific expression gene Nmnat in heart failure. The function of the gene in the adult heart is not reported until now on account of the lack of genetically modified animal models. The applicant found that the Nmnat gene might be involved in heart failure. Thus, we generated adult-cardiac specific Nmnat knockdown drosophila for the first time. In this study, we attempt to study the relation between Nmnat gene and the occurrence of heart failure, its role in the course of heart failure, the possible signaling pathway and the potential transcriptional regulation mechanism of heart failure. What is more, we attempt to explore and establish protective mechanisms in heart failure by combining human kinesiology and genetics. In conclusion, to establish the animal model of heart failure has important significance for investigating “the etiology-mechanism-prevention and treatment” of heart failure based on physical exercise.