Sustained treatment of sickle cell mice with haptoglobin increases HO-1 and H-ferritin expression and decreases iron deposition in the kidney without improvement in kidney function.
Sustained treatment of sickle cell mice with haptoglobin increases HO-1 and H-ferritin expression and decreases iron deposition in the kidney without improvement in kidney function.
复制标题
用结合珠蛋白持续治疗镰状细胞小鼠会增加 HO-1 和 H-铁蛋白的表达，并减少肾脏中的铁沉积，但肾功能没有改善。
DOI：
10.1111/bjh.14280
复制
发表时间：
2016
影响因子：
6.5
通讯作者：
Vercellotti,GregoryM
中科院分区：
文献类型：
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作者：
Shi,PatriciaA;Choi,Erika;Chintagari,NarendranathR;Nguyen,Julia;Guo,Xinhua;Yazdanbakhsh,Karina;Mohandas,Narla;Alayash,AbduI;Manci,ElizabethA;Belcher,JohnD;Vercellotti,GregoryM
越来越多的证据表明，细胞外血红蛋白和血红素在镰状细胞疾病中介导炎症和氧化损伤。结合珠蛋白(Hp)是游离血红蛋白的清除剂，在大多数因慢性溶血而患镰状细胞病的患者中是耗尽的。尽管单次注射幽门螺杆菌可以改善镰状细胞病小鼠模型的血管闭塞，但先前的研究还没有检验更多长期注射幽门螺杆菌对镰状细胞病表现的疗效。在本研究中，我们探讨了两种给药方案对镰刀鼠在3个月内的治疗效果：第一种是中剂量200 mg/kg，每周三次；第二种是高剂量，400 mg/kg，每周三次。我们发现，只有较高剂量的方案导致血红素加氧酶-1和重链铁蛋白(H-铁蛋白)的表达增加，并减少了肾脏中铁的沉积。尽管HP治疗后肾脏铁沉积减少，但肾功能没有明显改善。然而，有一个几乎显著的趋势是减少肝梗死。
There is growing evidence that extracellular haemoglobin and haem mediate inflammatory and oxidative damage in sickle cell disease. Haptoglobin (Hp), the scavenger for free haemoglobin, is depleted in most patients with sickle cell disease due to chronic haemolysis. Although single infusions of Hp can ameliorate vaso‐occlusion in mouse models of sickle cell disease, prior studies have not examined the therapeutic benefits of more chronic Hp dosing on sickle cell disease manifestations. In the present study, we explored the effect of Hp treatment over a 3‐month period in sickle mice at two dosing regimens: the first at a moderate dose of 200 mg/kg thrice weekly and the second at a higher dose of 400 mg/kg thrice weekly. We found that only the higher dosing regimen resulted in increased haem‐oxygenase‐1 and heavy chain ferritin (H‐ferritin) expression and decreased iron deposition in the kidney. Despite the decreased kidney iron deposition following Hp treatment, there was no significant improvement in kidney function. However, there was a nearly significant trend towards decreased liver infarction.