Peroxidation, vitamin E, and sickle-cell anemia.
Peroxidation, vitamin E, and sickle-cell anemia.
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过氧化、维生素 E 和镰状细胞性贫血。
DOI：
10.1111/j.1749-6632.1982.tb31272.x
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发表时间：
1982
影响因子：
5.2
通讯作者：
Lubin,B
中科院分区：
文献类型：
--
作者：
Chiu,D;Vichinsky,E;Yee,M;Kleman,K;Lubin,B
镰状细胞性贫血 (SCA) 是一种由 DNA 点突变引起的遗传性疾病，该突变在血红蛋白四聚体的 & 球蛋白链的第六个位置编码缬氨酸而不是谷氨酸。脱氧后，这种氨基酸取代会导致镰状血红蛋白聚合并形成细丝，最终将红细胞扭曲成特征性的镰状红细胞。这个过程被称为镰状化，当血红蛋白重新氧合时是可逆的。然而，在镰状化和去镰状化的重复循环中，红细胞膜被损坏并且不再允许细胞恢复到双凹形状。这些不可逆变形的细胞被称为不可逆镰状细胞（ISC）。尽管ISCs被认为影响SCA的临床严重程度，但导致体内ISCs形成的确切因素尚未确定。SCA的临床表现以慢性溶血性贫血、反复发生的血管闭塞性疼痛发作、频繁的细菌感染等为特征。在某些情况下，最终会丧失器官功能。然而，这种疾病存在明显的临床多样性。例如，一些镰状细胞病患者存在许多血管闭塞危象，需要频繁输血和住院治疗，而其他患者则很少出现并发症。尽管毫无疑问 SCA 的分子缺陷在于血红蛋白，但必须考虑其他或次要因素来解释这些不同的临床表现。这些因素之一可能与膜过氧化损伤及其对 SCA 病理生理学的影响有关。
Sickle-cell anemia (SCA) is a genetic disorder caused by a point mutation in DNA that codes for valine rather than glutamic acid in the sixth position of the &globin chain of the hemoglobin tetramer. Upon deoxygenation, this amino acid substitution causes sickle hemoglobin to polymerize and form filaments, which eventually distort the red cell into the characteristic sickle-shaped red cells. This process is referred to as sickling and is reversible when the hemoglobin is reoxygenated. However, upon repeated cycles of sickling and unsickling, the red cell membrane becomes damaged and no longer permits the cell to return to a biconcave shape. These irreversibly deformed cells are called irreversibly sickled cells (ISCs). Although ISCs are believed to influence clinical severity in SCA, the precise factors that contribute to formation of ISCs in vivo have not been established.The clinical manifestations of SCA are characterized by chronic hemolytic anemia, recurrent vasoocclusive painful attacks, frequent bacterial infections, and. in some cases, eventual loss of organ function. However, a marked clinical diversity exists in this disease. For instance, some sickle-cell patients have many vasoocclusive crises and require frequent blood transfusions and hospitalizations while others rarely have complications. Although there is little doubt that the molecular defect of SCA resides in the hemoglobin, additional or secondary factors must be considered to explain these diverse clinical manifestations. One of these factors may relate to membrane peroxidative damage and its effects on the pathophysiology of SCA.