Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
Center for Translational and International Hematology, Vascular Medicine Institute, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Br J Haematol. 2018 Jul;182(2):271-275. doi: 10.1111/bjh.15401. Epub 2018 Jun 19.
Acute chest syndrome (ACS) mortality in sickle cell disease (SCD) rises sharply in young adult patients and mechanism-based prophylaxis is lacking. In SCD, haem oxygenase-1 (HO-1) declines with age and ACS is associated with low HO-1. To test if enhanced HO-1 can reduce ACS mortality, young SCD mice were treated with D3T (3H-1,2-dithiole-3-thione), an activator of nuclear-factor erythroid 2 like 2, which controls HO-1 expression, for 3 months. Following haem-induced ACS, all vehicle-treated mice succumbed to severe lung injury, while D3T-treated mice had significantly improved survival. Blocking HO-1 activity abrogated the D3T effect. Thus HO-1 may be targeted to reduce ACS severity in adult patients.
镰状细胞病（SCD）患者的急性胸部综合征（ACS）死亡率在年轻成年患者中急剧上升，且缺乏基于机制的预防措施。在 SCD 中，血红素加氧酶-1（HO-1）随年龄下降，ACS 与低 HO-1 相关。为了测试增强 HO-1 是否可以降低 ACS 死亡率，用 3H-1,2-二硫杂环戊烷-3-硫酮（D3T）处理年轻的 SCD 小鼠 3 个月，这是一种核因子红细胞 2 样 2 的激活剂，可控制 HO-1 的表达。在诱导 ACS 后，所有接受载体治疗的小鼠均因严重的肺部损伤而死亡，而接受 D3T 治疗的小鼠的存活率则显著提高。阻断 HO-1 活性则消除了 D3T 的作用。因此，HO-1 可能成为降低成年患者 ACS 严重程度的靶点。
