Na+/K+-ATPase DR region antibody ameliorated cardiac hypertrophy and fibrosis in rats with 5/6 nephrectomy
Na+/K+-ATPase DR region antibody ameliorated cardiac hypertrophy and fibrosis in rats with 5/6 nephrectomy
复制标题
DOI：
10.1177/15353702221108910
复制
发表时间：
2022-07
影响因子：
3.2
通讯作者：
Jin Zheng;Ping Lan;Xun Meng;Min-chao Kang;Xin Huang;Xiaofei Yan
中科院分区：
文献类型：
--
作者：
Jin Zheng;Ping Lan;Xun Meng;Min-chao Kang;Xin Huang;Xiaofei Yan
Na+/K+-ATP 酶 (NKA) 在心脏中很重要。在慢性肾病（CKD）相关的心脏损伤中经常观察到 NKA 活性和表达的降低。此前，我们课题组发现靶向NKA1α1亚基DR胞外区的抗体（897DVEDSYGQQWTYEQR911）可刺激NKA活性，对缺血性损伤和异丙肾上腺素诱导的心脏重塑产生心脏保护作用。在这里，我们评估了 DRm217（一种特异性 DR 抗体）是否在慢性肾衰竭模型中表现出心脏保护作用。在 Sprague Dawley 大鼠模拟 CKD 的 5/6 肾切除术 (5/6 Nx) 手术中，我们观察到 5/6 Nx 大鼠心脏中的 NKA 活性和表达受到抑制。 DRm217 是一种 NKA DR 区抗体，可在 5/6 Nx 条件下减轻心脏肥大和心脏纤维化。进一步的研究表明，DRm217 在 5/6 Nx 条件下抑制 Src 激活并降低心脏中的活性氧 (ROS) 水平。我们的研究结果表明 NKA 可能成为 CKD 相关心脏病的治疗靶点。通过 DRm217 预防 CKD 引起的心肌损伤提供了一种有吸引力的治疗选择。
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 (897DVEDSYGQQWTYEQR911) 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.