前期研究表明：在心肌缺血再灌注损伤(MIRI)病理过程中，天麻素通过调控哺乳动物雷帕霉素靶蛋白(mTOR)相关通路磷脂酰肌醇3－激酶/蛋白激酶B(PI3-K/Akt)信号和AMP活化蛋白激酶/Sir2哺乳动物同源物(AMPK/SIRT1)信号发挥心肌保护的作用，但天麻素调控 mTOR 的中心靶蛋白的信号网络机制不清楚。本项目拟采用可诱导、细胞特异基因敲除的小鼠与细胞模型，使小鼠心肌细胞、血管内皮细胞和血管平滑肌细胞的 mTOR 复合物-1(mTORC1)被特异性地激活或抑制，深入研究 mTORC1 在天麻素治疗MIRI中对调控上述细胞的增殖、炎性反应、自噬与凋亡的信号网络机制。从分子、细胞和整体层面探讨 mTORC1 通路在天麻素治疗 MIRI 中的关键性作用，为临床应用天麻素治疗 MIRI 提供新的靶点与新的分子机制。同时，为进一步拓展云南优势特色天然药物新用途提供坚实的理论依据。

According to the World Health Organization, acute coronary occlusion is the leading cause of morbidity and mortality in the world and will continue to be the major cause of death in the world by the year 2020. Reperfusion therapy is beneficial to prevent cardiomyocyte death and contractile dysfunction after myocardial infarction (MI). However, numerous studies have shown that reperfusion itself may enhance the injury, resulting in extension of infarct size after ischemia, and termed myocardial ischemia/reperfusion injury (MIRI). Currently, it has been widely accepted that cardiac ischemic preconditioning (IPC) and ischemic postconditioning (IPost) can attenuate both contractile dysfunction and development of myocardial infarction following an MIRI insult. However, IPC and IPost have their limitations in that pre- and post-conditioning mimetic must be applied before and after the index ischemic event, which are unpredictable and impractical in the clinical setting of acute myocardial infarction. Accordingly, pharmacological pre- and post-conditioning were developed. Therefore, the identification and characterisation of agents that can protect the heart from the damaging effects of MIRI are of considerable importance..Gastrodin might play an important role in the protection against cardiovascular diseases, but its role and signal transduction pathway in anti-pathogenesis of myocardial ischemia/reperfusion injury (MIRI) have remained unexplored. Our preliminary results suggested that gastrodin regulated phosphoinositide 3-kinase (PI3-K) / protein kinase B (PKB) signaling and AMP-activated protein kinase (AMPK) / a mammalian ortholog of Sir2 (SIRT1) signaling-related mTOR signaling in the pathogenesis of MIRI. The current project aims to identify the roles and molecular and cellular mechanims of gastrodin on mammalian target of rapamycin complex 1 (mTORCI) signaling which plays a crucial role in determinating others signal transduction pathway in the anti-pathogenesis of MIRI. The inducible and cell-specific knockout mice and cellular models will be used, in which the mTORCI in cardiomyocytes, vascular endothelial cells and vascular smooth muscle cells in mice could be specifically activated or inhibited. The effects of mTORCI on proliferation, autophagy and apoptosis of these cells, secretion of cytokines and inflammatory factors and signaling pathways in the gastrodin-treated mice and cellular models will be investigated..Taking together, the research further our knowledge regarding the pathways used by gastrodin in exerting its protective effects and support our belief that gastrodin may hold future clinical promise in the development of novel therapeutic strategies for the treatment of MIRI. Furthermore, the research will provide experimental evidence for the novel application of natural products of Yunnan Province.