缺血/再灌注（I/R）是心肌损伤的主要原因，增强Na+-K+-ATPase（NKA）活性是治疗心肌I/R损伤的潜在靶点，但缺乏有效的激动剂。我们前期发现，针对NKA DR区段的抗体（DR抗体）能够增强NKA活性，稳定其在心肌细胞膜的表达。本课题拟在大鼠心肌细胞和组织I/R损伤模型中，检测DR抗体的保护作用以及NKA活性和细胞膜表达；通过多种分子手段筛查影响NKA活性及细胞膜表达的关键因子，分析DR抗体作用途径；从已知的I/R损伤机制入手，筛查DR抗体保护心肌的关键因子，抑制剂或激动剂干预关键因子，确定DR抗体作用的信号通路和分子机制；分析NKA激活或抑制在I/R损伤中的作用及信号通路差异点，在细胞和组织中进行反向验证，阐释激动或抑制NKA调控I/R损伤机制。课题研究不仅能获得预防I/R损伤的靶向分子，拓宽NKA在缺血/再灌注中的作用机制，也为阐明I/R损伤发生机制提供新思路。

Ischemia-reperfusion (I/R) is the main reason for myocardial injury; the underlying mechanisms are not fully uncovered. Improvement Na+-K+-ATPase (NKA) activity are a potent target for treating I/R injury. However, this research has been in a blank because no effective agonist can be used to enhance NKA activity. Our previous study has found that NKA DR region specific antibody (DR-Ab) stimulated NKA activity, stabilized NKA membrane expression. Based on the previous work, the following subjects will be investigated in this present project: 1), confirming the protective effects of DR-Ab on both in vivo and in vitro cardiac ischemia-reperfusion injury model and detecting NKA activity and membrane expression in these model; 2), detecting which factors influence NKA activity and membrane expression, analyze the origin of DR-Ab protect effect; 3) screening the important factors that influence DR-Ab protecting effect, interfere these factors to examine the underlying mechanisms and signaling pathway of DR-Ab protect effect; 4) inhibit or activate NKA activity in I/R injury model, analyses the different signaling pathway between two models and confirm it, thus elucidate the molecular mechanism between NKA and I/R injury. These results will confirm a specific molecular target for protecting I/R injury, deepen NKA role in I/R injury and provide new strategy for the prevention and cure of I/R injury.