基于myosin II-actin相互作用途径探讨生脉散活性成分群 抑制线粒体裂分介导心肌凋亡的机制

前期课题组应用正交实验、均匀实验设计及定量药理学等方法，从临床防治心肌缺血性疾病疗效确切的经典方剂生脉散中筛选发现一活性成分群，并在多种心肌缺血模型下证实其药效与生脉散作用相当。本项目基于线粒体裂分是心肌缺血再灌注损伤的关键病理环节，myosin II-actin相互作用可介导肿瘤细胞线粒体裂分，以及活性成分群影响myosin II的前期基础，提出“生脉活性成分群通过干预myosin II-actin相互作用途径，抑制线粒体裂分介导的心肌凋亡”的研究假说，综合采用RNA干扰、过表达、免疫荧光、邻位连接技术等多种分子生物学手段，确证myosin II与actin相互作用在心肌缺血再灌注损伤诱导线粒体裂分中的重要功能，并从整体、细胞、分子等多层面阐释该成分群发挥心肌保护效应的机制；以期为心肌缺血再灌注损伤的防治提供线索，为进一步揭示生脉散防治心血管疾病的作用特点，指导其临床合理应用提供参考依据

The combination of bioactive components derived from ShengMai San was obtained by orthogonal test, uniform design and quantitative pharmacology, which showed a significant protective effect on myocardial ischemia injury in experimental studies. And the efficacy of the combination was similar to ShengMai San under a variety of myocardial ischemia models. This research chooses the mitochondrial fission mediated myocardial apoptosis, which plays an important role in myocardial ischemia reperfusion, and the interaction of myosin II and actin as the breakthrough point. We hypothesize that " The combination of bioactive components derived from ShengMai San modulates the interaction of myosin II and actin, then inhibits the mitochondrial fission-mediated myocardial apoptosis ". The modern molecular biology methods of siRNA, over-expression, immunofluoresence, proximity ligation assay, and so on, are used to study the interaction of myosin II and actin in mitochondrial fission and the regulation role of bioactive components derived from ShengMai San. This study will provide a better understanding of the characteristics and signaling pathways of ShengMai San in prevention and treatment of myocardial ischemic disease and offer new treatment strategies for myocardial ischemia reperfusion injury.