我们前期研究发现sRAGE通过抑制心肌细胞凋亡拮抗I/R损伤。UPS是清除细胞内受损蛋白的另一重要途径，我们前期工作发现I/R损伤可抑制心肌组织中UPS活性，而sRAGE可以增加UPS活性，因此我们推测sRAGE通过激活心肌细胞内UPS，增强细胞清除受损蛋白的能力，减少心肌细胞凋亡，起到保护心肌I/R损伤的作用。本项目拟通过观察I/R时sRAGE、UPS和心肌细胞凋亡的变化；sRAGE对I/R时UPS和心肌细胞凋亡的影响；干预UPS对sRAGE上述作用的影响；以及相关信号转导通路的变化，验证sRAGE通过激活UPS，减少心肌细胞凋亡发挥其心脏保护作用的假说。

Severe myocardial dysfunction and tissue damage resulting from ischemia reperfusion is a common clinical scenario in patients with certain types of heart diseases and therapies such as thrombolysis, percutaneous coronary intervention,coronary artery bypass grafting, and cardiac transplantation. The underlining mechanism of endogenous cardiac protection after ischemia reperfusion injury has been a focus of current research.Growing evidences suggests that soluble receptor for advanced glycation end-products has a cardioprotective effect; however, its role in ischemia reperfusion injury remains unclear.Our previous study found that soluble receptor for advanced glycation end-products (sRAGE) could prevent from ischemia reperfusion injury through alleviating apoptosis of cardiomyocyte. The ubiquitin proteasome system is another important way of clearing away the damaged protein in the cell. Our previous work has found that ischemia reperfusion injury could inhibit activities of ubiquitin proteasome system (UPS) in the cardiomyocytes, while sRAGE can increase activities of the UPS. Our hypothesis is that sRAGE can protect the heart through activating UPS which could reduce apoptosis of cardiomyocyte. Our study included observing change of endogenous sRAGE, UPS, apoptosis in cardiomyocytes and effect of sRAGE on UPS, apoptosis when ischemia reperfusion injury happened and effect of sRAGE when activating or inhibiting UPS. The project will provide new thought for clarifying mechanism of myocardial ischemia reperfusion in patients with coronary heart disease and for prevention and treatment of the disease.