基于Wnt/β-catenin信号通路研究活心丸抑制急性心肌缺血中炎症反应的作用机制

急性心肌缺血（AMI）导致的心衰和高死亡率严重威胁人类健康。大量研究表明抗炎策略有望改善AMI预后。前期研究发现靶向抑制AMI后激活的Wnt/β-catenin通路可改善心功能和预后。临床表明活心丸治疗冠心病疗效确切但机制未明。预实验显示Wnt/β-catenin通路强烈诱导NF-κB激活且活心丸可通过抑制Wnt/β-catenin通路而改善心功能及下调炎症下游基因。因此提出“活心丸通过抑制AMI后激活的Wnt/β-catenin通路诱导的炎症而阻止心脏过度重塑是其发挥疗效的机制”的假说，以期证明靶向抑制Wnt/β-catenin通路所控制的炎症通路是治疗急性心肌缺血有效的抗炎策略。本课题拟通过AMI疾病模型、双报告基因、Real-time PCR、蛋白印迹、IHC和心超等方法探讨活心丸对改善AMI预后的机制，以期阐明活心丸治疗缺血性心脏病的分子机制和作用靶点，为临床应用提供理论依据。

Heart failure induced by acute myocardial ischemia (AMI) are associated with high mortality, which heavily threatens the quality of life of affected patients. Numerous clinical studies have showed that anti-inflammation is a viable strategy for improving prognosis in patients with AMI. We had previously shown that targeted inhibition of Wnt/β-catenin pathway can meliorate heart function and improve prognosis following myocardial infarction. Clinical studies have also shown that the traditional Chinese medicine, Huo Xin Wan definitely has beneficial medical outcome of coronary heart disease, although the underlying mechanism remain elucidated. Our preliminary experiments indicated that activation of Wnt/β-catenin pathway robustly promoted the nuclear translocation of NF-κB. Furthermore, treatment with Huo Xin Wan significantly protected against myocardial infarction-induced reduction in heart function, and robustly decreased the expression of inflammatory target genes via inhibition of Wnt/β-catenin pathway. Therefore, we proposed the hypothesis that Huo Xin Wan can lessen inflammation and subsequent attenuate cardiac remodeling via inhibition of Wnt/β-catenin pathway following AMI. Furthermore, we proposed that targeted inhibition of Wnt/β-catenin pathway induced inflammation signals is an effective and novel strategy for anti-inflammation therapy. We utilized multiple molecular techniques such as murine models of myocardial infarction, Luciferase double-reporter gene assays, Immunohistochemical assays, Real-time PCR, Western blots and heart echocardiography examinations, in order to determine the underlying molecular mechanisms and therapeutic targets of Huo Xin Wan in improving the prognosis of AMI. Thus, this study provides a theoretical basis for the clinical use of Huo Xin Wan as an effective treatment for AMI.