增强细胞膜上钠钾ATP酶(NKA)的表达是抑制心梗后心室重构（VR）的潜在靶点。NKA磷酸化降低细胞膜上NKA的表达，然而促进NKA去磷酸化能否抑制心梗后VR尚不清楚。我们发现DRmAb单抗增强NKA与PP2A的结合，稳定细胞膜上NKA的表达。拟用冠脉结扎建立心梗后VR动物模型，研究DRmAb的保护作用及与NKA、PP2A的相关性；再用AngII刺激细胞，PP2A抑制剂和DRmAb作用下，研究PP2A介导的NKA去磷酸化对DRmAb抑制心肌肥大和纤维化作用的调控；进而用分子生物学和信息学方法，研究NKA与PP2A的结合部位和NKA去磷酸化位点，细胞上检测NKA相应位点突变对心肌肥大、纤维化的作用和分子机制；最后用基因干预和药理学方法，通过在体实验，检测PP2A抑制、NKA磷酸位点突变对心梗后VR的影响。结果将阐明NKA去磷酸化对心梗后VR的抑制作用和分子机制，获得预防心梗后VR的靶分子。

Stabilization of Na+/K+-ATPase’s (NKA) membrane expression is a potential target on inhibition of MI-VR. Though it has proved that phosphorylation of NKA reduced the membrane expression of NKA, but whether dephosphorylation of NKA can inhibit the development of MI-VR is still unknown. Our previous study has found that NKA DR region specific monoclonal antibody（DRmAb）enhanced NKA-PP2A protein interaction and stabilized the membrane expression of NKA. In the present project, we will firstly establish MI-VR model by ligation of coronary artery, observe the effect of DRmAb on ventricular remodeling and the expression of NKA and PP2A, analysis whether the protective effect of DRmAb has relevance with NKA and PP2A. Then we will induce cell model of cardiac hypertrophy and cardiac fibrosis by AngII treatment, observe the cell morphology, the expression of m-NKA，p-NKA and the protein interaction between NKA and PP2A in cell models treated with PP2A inhibitor and DRmAb, verify the role of PP2A-induced dephosphorylation of NKA in the protective effect of DRmAb on cardiac hypertrophy and cardiac fibrosis. Then we will construct truncated NKA, detect the binding site of NKA and PP2A by GST pull down and yeast two-hybrid system, analysis the dephosphorylation site of NKA by bioinformatics methods, detect whether mutation of NKA’s dephosphorylation site can inhibit cardiac hypertrophy and cardiac fibrosis and detected NKA/Src signal pathway in it. Finally, we will inhibit PP2A function or mutate NKA dephosphorylation site by using PP2A inhibitor or adeno-associated virus in vivo, observe the effect of inhibition of PP2A or mutation of NKA’s dephosphorylation site on the development of Mi-VR. These results will help us reveal the function of DRmAb in MI-VR, clarify the precise molecular mechanism of dephosphorylation of NKA in the development of MI-VR, and provide the novel targets in the treatment of MI-VR.