心脏缺血再灌注损伤是导致缺血性心脏病预后不良的主要原因之一，有效药物干预是对抗心肌缺血再灌注损伤的重要策略。本课题组已经证明1-磷酸鞘氨醇（S1P）具有缺血心肌保护作用，但由于受代谢等因素的影响，外源性给予S1P应用于临床还未成为可能。本研究旨在探讨S1P受体激动剂FTY720在心脏缺血再灌注损伤中的保护作用，拟建立大鼠心肌再灌注损伤的在体，离体心脏模型，心肌细胞模型，应用蛋白印迹法检测凋亡信号传导通路的变化，应用定量PCR方法检测线粒体功能，应用心脏超声方法检测心功能，应用细胞计数法检测细胞存活率，ELISA方法检测心肌酶学变化。本课题希望研究证明S1P受体激动剂FTY720，通过兴奋S1P受体，激活一系列的信号传导通路，在缺血再灌注心肌损伤中起保护作用，并且揭示其作用相关机制，为缺血再灌注心肌损伤寻找新的药物靶点。

Ischemia-reperfusion injury is one of the main reasons for poor clinical treatment of ischemic heart disease. Effective medicine is a crucial strategy to fight against ischemia-reperfusion injury. Studies have showed that sphingosine 1 phosphate (S1P) may have protective effect on ischemic heart disease. Due to the influence of metabolic factors, exogenous S1P applied in clinic is not possible. In order to explore the role of S1P receptor agonist FTY720 on myocardial ischemia-reperfusion injury, we intend to establish the rat ischemia/reperfusion model in vivo, in isolated heart and in myocardial cells. Western blots will be used to measure apoptosis signaling pathway. Quantitative PCR method will be used to detect mitochondrial function. Echocardiography will be used to measure cardiac function, Survival rate of cells will be checked by cell counting method. ELISA method will be used to detect the changes of myocardial enzyme. In this study we hope to show the S1P receptor agonist FTY720, through activating the S1P receptors, activating signal transduction pathways in a series, plays a protective role in myocardial ischemia reperfusion injury. We try to provide a sufficient theoretical basis of the further development and clinical application of ischemic heart disease.