Steinberg Martin H
Boston University School of Medicine, Room E211, 88 East Newton Street, Boston, MA 02118, USA.
Curr Hematol Rep. 2003 Mar;2(2):95-101.
The pathophysiology of sickle cell disease originates in the polymerization of sickle hemoglobin. Fetal hemoglobin (HbF) inhibits this process, and high HbF concentrations reduce the severity of the disease. Drugs with presumed mechanisms of action that perturb the orderly maturation of erythroid precursor cells, induce hypomethylation of HbF genes, bind transcriptionally active elements of these genes, or influence chromatin structure can enhance HbF production in sickle cell disease. Hydroxyurea, a drug that affects erythroid maturation and regeneration, reduces morbidity and mortality in adults with sickle cell anemia. Its use in young children and in combination with other classes of HbF-inducing agents is being studied.
镰状细胞病的病理生理学源于镰状血红蛋白的聚合。胎儿血红蛋白（HbF）可抑制这一过程，高浓度的HbF可减轻疾病的严重程度。作用机制推测为干扰红系前体细胞有序成熟、诱导HbF基因低甲基化、结合这些基因的转录活性元件或影响染色质结构的药物，可增加镰状细胞病患者的HbF生成。羟基脲是一种影响红系成熟和再生的药物，可降低镰状细胞贫血成人患者的发病率和死亡率。目前正在研究其在幼儿中的应用以及与其他类HbF诱导剂联合使用的情况。
