Sirtuins蛋白家族被发现在心肌保护方面具有重要作用，在中药药效物质发现领域引起了广泛关注，但其活性和调节剂的研究尚处于起步阶段。课题组在前期研究中，以方剂生脉方为研究对象，利用靶向SIRT1荧光探针技术初步发现了多个具有保护心肌细胞的SIRT1激动剂。为此，本课题拟在前期研究基础上，系统开发能够用于心肌保护物质发现的Sirtuins点亮型近红外荧光探针。该探针有望克服现有Sirtuins探针特异性低、发射波长短等不足，能够有效避免复杂体系背景荧光的干扰，且具有生物相容性高、细胞毒性低的优点。本项目拟利用荧光探针通过分子－细胞－整体水平实验，筛选发现其中活性物质，并在多层次动物模型上对其进行药效学验证，进而绘制多种药效物质对心肌的保护作用谱，进而阐释中药药效物质作用机制。此研究对于在分子层面理解益气活血中药防治心血管复杂疾病的科学内涵，推动相关中药品种的临床应用具有重要价值。

Sirtuins play an important role in myocardial protection, which have attracted extensive attentions in the fields of the discovery of effective constituents from traditional Chinese medicines(TCMs), but the research on its activity and regulators is still in the initial stage. In the previous study, we got several myocardial protective substances from Shengmai formula by the fluorescence probe targeting SIRT1. Recently, on the basis of previous research, this project plans to systematically develop light-up near-infrared fluorescent probes targeting Sirtuins which can be used for screening myocardial protective substances from Yi-Qi-Huo-Xue TCMs. These probes will be able to overcome the defects such as low specificity and short emission wavelength, effectively avoid the interference of background fluorescence from complex systems and have advantages of high biocompatibility and low cytotoxicity. In this project, we intend to use fluorescent probes to screen and find the active substances from Yi-Qi-Huo-Xue TCMs at molecular and cell levels, and verify their pharmacodynamics on the multi-level animal model, then draw the regulatory action spectrum of various active substances on myocardial protection, which can explain the mechanism of action of TCMs. This study is of great value to understand the scientific connotation of Yi-Qi-Huo-Xue TCMs in the prevention and treatment of cardiovascular complex diseases at the molecular level and to promote the clinical application of related Chinese medicine varieties.