罗沙司他：一种在MHD患者左心室肥厚治疗方面具有潜在应用价值的低氧诱导因子脯氨酰羟化酶抑制剂

王 生香, 巴应 贵*
青海大学附属医院临床医学院

摘要


维持性血液透析（MHD）作为一种技术成熟的肾脏替代治疗方式，被大多数终末期肾病患者所选择。MHD的并发症常见有高血压、心力衰竭、心律失常、贫血、肾性骨病等，在疾病的终末期大多会发展为心血管疾病（CVD），这也是MHD临床致死率高的主要原因。而左心室肥厚（LVH）和心肌纤维化为特征的心脏重构极为常见，会导致心血管疾病的发病率和死亡率增加。MHD患者并发左心室肥厚的发病机制涉及多种病理过程，包括压力负荷、容量负荷过重、RAAS系统激活、甲状旁腺素（PTH）升高、氧化应激和炎症反应损伤心肌、钙磷代谢异常等。低氧诱导因子（HIF）信号通路在上述过程中均发挥着重要作用。本综述总结了罗沙司他是低氧诱导因子-1α（HIF-1α）的激活剂，它通过抑制低氧诱导因子脯氨酰羟化酶（HIF-PHD）来增加HIF-1α的转录活性。罗沙司他通过激活血管内皮生长因子（VEGF）、毛细血管生成素-2（Ang-2）、调控TGF-B1/Smad3等下游信号通路和降低铁调素、减少氧化应激、稳定心脏能量代谢等方法，在改善左心室肥厚方面发挥调节作用。我们试图更全面地揭示罗沙司他的治疗效果，为其在MHD患者并发症左心室肥厚治疗方面的进一步研究提供参考。

关键词


罗沙司他；左心室肥厚（LVH）；心血管疾病（CVD）；低氧诱导因子

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参考


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