心肌梗死是指急性、持续性缺血、缺氧所引起的心肌坏死,也是我国死亡率最高的疾病之一。而缺血后的再灌注(I/R)会对心肌产生缺血/再灌注损伤，研究认为细胞内钙超载是I/R损伤发生的主要机制之一。细胞内Cl-浓度（[Cl-]i）的调节对于人体各个器官组织细胞的正常生理过程很重要的，而关于心肌细胞如何调控Cl-的稳态，目前知之甚少。本课题组前期研究表明，WNK-SPAK信号通路调控KCC3 和NKCC1在维持上皮细胞内Cl-离子平衡以及细胞体积发挥重要作用。本研究将探讨KCC3在小鼠心肌组织的分布和正常生理作用，还将在整体动物水平研究WNK1-SPAK信号通道调控KCC3 和NKCC1在维持心肌细胞Cl-稳态在心肌缺血损伤中的作用机制及靶向药物干预。以上研究将为阐明心肌细胞如何调控Cl-稳态的分子机理提供理论依据，为心肌梗死的预防和新药开发提供方案。

Myocardial infarction refers to myocardial necrosis caused by acute, persistent ischemia and hypoxia, and it is one of the diseases with the highest mortality rate in China. Ischemic reperfusion (I/R) can cause ischemia/reperfusion injury to the myocardium. It is considered that intracellular calcium overload is one of the main mechanisms of I/R injury. The regulation of intracellular Cl-concentration ([Cl-]i) is important for the normal physiological processes of cells in various organs of the human body, however little is known about how cardiomyocytes regulate the homeostasis of Cl-. Previous studies by our group have shown that WNK-SPAK signalling pathway regulates KCC3 and NKCC1 to play an important role in maintaining Cl- ion balance and cell volume in epithelial cells. We will investigate the distribution and normal physiological effects of KCC3 in mouse myocardial tissue. We will also study the mechanism of WNK1-SPAK signalling pathway regulating KCC3 and NKCC1 in maintaining cardiomyocyte Cl- steady state in myocardial ischemic injury at the overall animal level, and targeted drug intervention. This proposed research will provide a theoretical basis for elucidating the molecular mechanism of how cardiomyocytes regulate Cl- steady state, and provide solutions for the prevention and treatment of myocardial infarction.