缺血再灌注损伤常伴随冠心病的发病过程，冠心病则是心衰的主要致病因素。线粒体是细胞重要的细胞器，是机体能量供应站、ROS产生主要部位、细胞内钙缓冲部位，以及细胞生存和死亡信号的调控中枢。心肌细胞中线粒体含量达细胞体积的40%以上，线粒体功能障碍与心肌缺血再灌注损伤密切相关。酪氨酸相互作用蛋白51(PTPIP51)位于线粒体，参与细胞多种生物学功能，如细胞增殖、分化、凋亡等，其异常与多种肿瘤及神经退行性病变相关。PTPIP51蛋白的心脏功能目前尚未可知。我们预实验发现，缺血再灌注心肌PTPIP51表达量明显增加；过表达PTPIP51诱导心肌细胞凋亡，敲低PTPIP51则抑制过氧化氢所致的细胞凋亡，提示PTPIP51在心脏中具有重要功能。本项目拟在心肌细胞、心脏缺血再灌注及心脏敲低PTPIP51小鼠模型中，深入探讨PTPIP51在心肌及缺血再灌注损伤心脏中的作用及作用机制。

Cardiac ischemia-reperfusion (I/R) injury usually accompanies with coronary heart disease which is one of the leading causes of heart failure. A variety of mechanisms, including ischemia/reperfusion-triggered excess reactive oxygen species (ROS) production, intracellular calcium overload, dysfunction of cardiac contractile activity, and necrotic or apoptotic cell death, have been proposed to explain cardiac dysfunction and subsequently pathological processes after cardiac ischemia/reperfusion. Mitochondria, the energy supplying organelle also as an important component of intracellular calcium buffering system, the primary resource of ROS production, as well as the central determinant of cell survival and death, are gradually recognized as a pivotal player in the genesis of ischemia/reperfusion injury. As a metabolically active tissue, heart cells contain prominent mitochondrial networks, occupying up to 40% of cell volume and generating ATP in response to energy needs through oxidative phosphorylation (OXPHOS). Dysfunctions of mitochondria, such as decreased mitochondrial electron transport chain activity and mitochondrial ATP synthesis, increased ROS production, the opening of the mitochondrial permeability transition pore (MPT), subsequent release of cytochrome C from mitochondria to cytosol, and eventually cell death, are closely associated with cardiac ischemia/reperfusion. ..Protein tyrosine phosphatase interacting protein 51 (PTPIP51) localizes on mitochondria and participates in multiple cellular processes including proliferation, differentiation and apoptosis. Dysfunction of PTPIP51 is associated with diseases such as cancers and neurodegenerative disorders. However, the cardiac function of PTPIP51 is still unclear. Our preliminary data showed that PTPIP51 protein has been upregulated in mouse ischemia/reperfusion hearts and in H2O2 treated cardiomyocytes, and overexpressing PTPIP51 led to cardiomyocytes apoptosis, while knockdown of PTPIP51 ameliorated H2O2-mediated apoptosis, indicating a pivotal role of PTPIP51 in cardiac ischemia/reperfusion. In the present study, by gain- and loss-of function approaches, we will investigate whether PTPIP51 regulates cardiac function during ischemia/reperfusion both in vitro and in vivo, and if so, to reveal the underlying mechanisms.