Hospital of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.
Exp Biol Med (Maywood). 2022 Oct;247(19):1785-1794. doi: 10.1177/15353702221108910. Epub 2022 Jul 14.
The enzyme Na/K-ATPase (NKA) is important in the heart. Reductions in NKA activity and expression have often been observed in chronic kidney disease (CKD)-related heart injury. Previously, our group found that an antibody targeting the NKA1α1 subunit's DR extracellular region (DVEDSYGQQWTYEQR) stimulated NKA activities and produced cardioprotective effects against ischemic injury and isoproterenol-induced cardiac remodeling. In here, we assessed whether DRm217, a specific DR antibody, exhibits cardioprotective effects in chronic renal failure models. In 5/6 nephrectomy (5/6 Nx) surgery to mimic CKD in Sprague Dawley rat, we observed that NKA activity and expression were depressed in the hearts of 5/6 Nx rats. DRm217, an NKA DR region antibody, alleviated heart hypertrophy and cardiac fibrosis under 5/6 Nx conditions. Further studies revealed that DRm217 inhibited Src activation and reduced reactive oxygen species (ROS) levels in hearts under 5/6 Nx conditions. Our findings imply that NKA could be a treatment target in CKD-related cardiac diseases. Prevention of CKD-induced myocardial injury by DRm217 provides an appealing therapeutic alternative.
钠钾泵（Na/K-ATPase，NKA）在心脏中发挥重要作用。在慢性肾脏病（chronic kidney disease，CKD）相关的心脏损伤中，通常观察到 NKA 活性和表达降低。此前，我们的研究小组发现，针对 NKA1α1 亚基 DR 细胞外区域（DVEDSYGQQWTYEQR）的抗体可刺激 NKA 活性，并对缺血性损伤和异丙肾上腺素诱导的心脏重构产生心脏保护作用。在这里，我们评估了针对 NKA DR 区的特异性抗体 DRm217 在慢性肾衰竭模型中是否具有心脏保护作用。在 5/6 肾切除术（5/6 Nx）手术中模拟 CKD 后，我们观察到 5/6 Nx 大鼠心脏中的 NKA 活性和表达降低。DRm217 是一种 NKA DR 区抗体，可减轻 5/6 Nx 条件下的心脏肥大和心脏纤维化。进一步的研究表明，DRm217 抑制了 5/6 Nx 条件下心脏中Src 的激活并降低了活性氧（ROS）水平。我们的研究结果表明，NKA 可能是 CKD 相关心脏疾病的治疗靶点。DRm217 预防 CKD 诱导的心肌损伤为治疗提供了一种有吸引力的替代方案。
