活心丸通过抑制Wnt/β-catenin通路阻止急性心肌缺血损伤的机制研究

急性心肌缺血(AMI)及其并发症是严重危害人类健康的心血管疾病。临床试验表明活心丸治疗冠心病疗效确切，但作用机制尚未完全阐明。本课题组前期研究发现AMI发生后早期激活的Wnt/β-catenin通路是心肌细胞发生氧化应激损伤的关键原因之一。因此通过靶向抑制AMI发生早期的Wnt/β-catenin通路激活可阻止心肌细胞进一步损伤。预实验显示活心丸可明显抑制Wnt/β-catenin通路，提示“活心丸抑制Wnt/β-catenin通路可能是其保护急性心肌缺血损伤的重要机制”。本课题拟通过急性心肌缺血动物模型，采用荧光素酶双报告基因、Real-time PCR、Western Blot和免疫组化等技术方法阐明活心丸对急性心梗损伤的保护机制，以期深入阐明活心丸治疗急性心肌缺血的分子机制和作用靶点，为临床应用提供理论依据。

Acute myocardial infarction (AMI) is a cardiovascular disease that is associated with numerous complications, which can significantly endanger human health. Clinical trials have shown that Huo Xin Wan can be effective in treating coronary heart disease, however, its mechanism has not yet been fully elucidated. Our previous study demonstrated that the activation of Wnt/β-catenin pathway at an early stage of AMI was one of the key causes of oxidative stress injury in cardiomyocytes. Therefore, inhibiting the early activation of Wnt/β-catenin pathway can theoretically prevent further damage to cardiac myocytes at an early stage of AMI. Our preliminary experiments indicate that Huo Xin Wan can significantly inhibits the Wnt/β-catenin pathway, which suggest that “Huo Xin Wan protects AMI injury by inhibiting Wnt/beta-catenin pathway maybe one of the underlying important mechanisms” . We therefore hope to elucidate the precise molecular mechanism of Huo Xin Wan in protecting against AMI injury using AMI animal models, luciferase double-reporter gene assays, Real-time PCRs, Western Blots and immunohistochemical assays both in vitro and in vivo, as well as its therapeutic targets, in order to provide a novel and promising means for the clinical treatment of AMI.